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Interaction between renin-angiotensin and sympathetic nervous systems in a rat model of pressure overload cardiac hypertrophy

Rathore HA, Munavvar AS, Abdullah NA, Khan AH, Fathihah B, NurJannah MH, et al.

Auton Autacoid Pharmacol, 2009 Oct;29(4):171-80.
PMID: 19740088 DOI: 10.1111/j.1474-8665.2009.00445.x

1 A raised cardiac workload activates neurohormones which will increase muscle mass and shift contractility to the right along the Frank-Starling curve. 2 This study examined the interaction between the SNS and RAS in contributing to vascular responsiveness following the development of cardiac hypertrophy due to aortic banding. 3 Sprague Dawley rats (180-200 g) were assigned to one of six groups; Normal, Sham-operated, Aortic Banded (AB), Aortic Banded treated with losartan (ABLOS), Aortic Banded treated with 6-hydroxydopamine (ABSYMP) and Aortic banded treated with both losartan and 6-hydroxydopamine (ABSYMPLOS). A constricting band was placed around the supra renal aorta on day zero with drug treatment from day 37 to day 44. Vasopressor responses to noradrenaline, phenylephrine, methoxamine and angiotensin II were measured on day 45. 4 The magnitudes of the MAP responses to all vasoactive agents, expressed as percentage changes, were similar in Normal and Sham groups, but reduced in the AB group. ABLOS group showed attenuated response to ANGII whereas all responses were enhanced in the ABSYM group. 5 A positive interaction between the two systems was observed with alpha(1A)-adrenoceptors identified as a major component of SNS and AT(1) receptors of RAS to induce vasopressor effects.

Matched MeSH terms: Sympathetic Nervous System/physiology*
Inhibition of Ang II and renal sympathetic nerve influence dopamine-and isoprenaline-induced renal haemodynamic changes in normal Wistar-Kyoto and spontaneously hypertensive rats

Abdulla MH, Sattar MA, Abdullah NA, Hazim AI, Anand Swarup KR, Rathore HA, et al.

Auton Autacoid Pharmacol, 2008 Oct;28(4):95-101.
PMID: 18778332 DOI: 10.1111/j.1474-8673.2008.00422.x

1. This study was undertaken to elucidate the effects of inhibiting the renin-angiotensin system (RAS) with losartan, and acute unilateral renal denervation on renal haemodynamic responses to intrarenal administration of vasoconstrictor doses of dopamine and vasodilator doses of isoprenaline in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). 2. Acute unilateral renal denervation of the left kidney in rats was confirmed by a drop in the renal vasoconstrictor response to renal nerve stimulation (P < 0.05) along with diuresis and natriuresis. Rats were pretreated with losartan for 7 days and thereafter animals fasted overnight were anaesthetized (sodium pentobarbitone, 60 mg/kg i.p.) and acute renal haemodynamic responses studied. 3. Dose-response curves were constructed for dopamine and isoprenaline that induced falls or increases in renal blood flow, respectively. It was observed that renal vascular responses were greater in the denervated as compared with rats with intact renal nerves (all P < 0.05). Dopamine-induced renal vasoconstrictor responses were markedly lower in losartan-treated denervated WKY and SHR compared with their untreated counterparts (all P < 0.05). It was also observed that in losartan-treated and denervated WKY rats the vasodilatory responses to isoprenaline were markedly lower compared with untreated rats (all P < 0.05). However, in SHR, under the same conditions, there was no difference in the renal response to isoprenaline whether or not rats were treated with losartan (P > 0.05). 4. The data obtained showed that the renal vasoconstrictor effect of dopamine depends on intact renal nerves and RAS in WKY and SHR. Isoprenaline responses were likewise sensitive to renal denervation and RAS inhibition in WKY rats but not SHRs. Our observations reveal a possible relationship between renal AT(1) receptors and alpha(1)-adrenoceptors in WKY and SHR. There is also evidence to suggest an interaction between renal beta-adrenoceptors and AT(1) receptors in WKY rats.

Matched MeSH terms: Sympathetic Nervous System/drug effects; Sympathetic Nervous System/physiology*; Sympathetic Nervous System/surgery
Role of supraspinal vasopressin neurones in the effects of atrial natriuretic peptide on sympathetic nerve activity

Yusof AP, Yusoff NH, Suhaimi FW, Coote JH

Auton Neurosci, 2009 Jun 15;148(1-2):50-4.
PMID: 19349212 DOI: 10.1016/j.autneu.2009.03.005

The aim of the present study was to determine if paraventricular-spinal vasopressin neurones participate in the sympatho-inhibitory effects of systemically administered atrial natriuretic peptide (ANP) on renal sympathetic nerve activity (RSNA). Experiments were carried out on male Sprague-Dawley rats anesthetized with 1.3 g/kg urethane. Changes in mean arterial pressure (mm Hg), heart rate (beats per minute) and RSNA (%) were measured following intravenous bolus administration of ANP (250 ng, 500 ng and 5 microg). Intrathecal application of selective V 1a receptor antagonist was performed to test for the involvement of supraspinal vasopressin pathways in mediating the effect on sympathetic outflow evoked by intravenous ANP administration. The results obtained demonstrated that both low and high doses of ANP caused renal sympathoinhibition (250 ng; - 7.5 +/- 1%, 500 ng; - 14.2 +/- 1%, 5 microg; - 16.4 +/- 2%), concomitant with vasodilation and bradycardia. After spinal vasopressin receptor blockade, the inhibitory effects of ANP were prevented and there was a small renal sympatho-excitation (250 ng; + 1.7 +/- 0.2%, 500 ng; + 6.1 +/- 0.03%, 5 microg; + 8.0 +/- 0.03%, P < 0.05). Therefore, the renal sympathetic nerve inhibition elicited by circulating ANP is dependent on the efficacy of a well established supraspinal vasopressin pathway. Since supraspinal vasopressin neurones without exception excite renal sympathetic neurones, it is suggested that ANP elicits this effect by activating cardiac vagal afferents that inhibit the spinally projecting vasopressin neurones at their origin in the paraventricular nucleus of the hypothalamus.

Matched MeSH terms: Sympathetic Nervous System/drug effects*; Sympathetic Nervous System/physiology
Tembusu-like flavivirus (Perak virus) as the cause of neurological disease outbreaks in young Pekin ducks

Homonnay ZG, Kovács EW, Bányai K, Albert M, Fehér E, Mató T, et al.

Avian Pathol, 2014;43(6):552-60.
PMID: 25299764 DOI: 10.1080/03079457.2014.973832

A neurological disease of young Pekin ducks characterized by ataxia, lameness, and paralysis was observed at several duck farms in Malaysia in 2012. Gross pathological lesions were absent or inconsistent in most of the cases, but severe and consistent microscopic lesions were found in the brain and spinal cord, characterized by non-purulent panencephalomyelitis. Several virus isolates were obtained in embryonated duck eggs and in cell cultures (Vero and DF-1) inoculated with the brain homogenates of affected ducks. After exclusion of other viruses, the isolates were identified as a flavivirus by flavivirus-specific reverse transcription-polymerase chain reaction (RT-PCR) assays. Inoculation of 2-week-old Pekin ducks with a flavivirus isolate by the subcutaneous or intramuscular route resulted in typical clinical signs and histological lesions in the brain and spinal cord. The inoculated virus was detected by RT-PCR from organ samples of ducks with clinical signs and histological lesions. With a few days delay, the disease was also observed among co-mingled contact control birds. Phylogenetic analysis of NS5 and E gene sequences proved that the isolates were representatives of a novel phylogenetic group within clade XI (Ntaya virus group) of the Flavivirus genus. This Malaysian Duck Tembusu Virus (DTMUV), named Perak virus, has moderate genomic RNA sequence similarity to a related DTMUV identified in China. In our experiment the Malaysian strain of DTMUV could be transmitted in the absence of mosquito vectors. These findings may have implications for the control and prevention of this emerging group of flaviviruses.

Matched MeSH terms: Nervous System Diseases/veterinary
Fulltext Cytotoxicity and apoptotic activities of alpha-, gamma- and delta-tocotrienol isomers on human cancer cells

Lim SW, Loh HS, Ting KN, Bradshaw TD, Zeenathul NA

BMC Complement Altern Med, 2014;14:469.
PMID: 25480449 DOI: 10.1186/1472-6882-14-469

Tocotrienols, especially the gamma isomer was discovered to possess cytotoxic effects associated with the induction of apoptosis in numerous cancers. Individual tocotrienol isomers are believed to induce dissimilar apoptotic mechanisms in different cancer types. This study was aimed to compare the cytotoxic potency of alpha-, gamma- and delta-tocotrienols, and to explore their resultant apoptotic mechanisms in human lung adenocarcinoma A549 and glioblastoma U87MG cells which are scarcely researched.

Matched MeSH terms: Central Nervous System Neoplasms/drug therapy*; Central Nervous System Neoplasms/metabolism
Fulltext Identification and validation of clinical predictors for the risk of neurological involvement in children with hand, foot, and mouth disease in Sarawak

Ooi MH, Wong SC, Mohan A, Podin Y, Perera D, Clear D, et al.

BMC Infect Dis, 2009 Jan 19;9:3.
PMID: 19152683 DOI: 10.1186/1471-2334-9-3

BACKGROUND: Human enterovirus 71 (HEV71) can cause Hand, foot, and mouth disease (HFMD) with neurological complications, which may rapidly progress to fulminant cardiorespiratory failure, and death. Early recognition of children at risk is the key to reduce acute mortality and morbidity.
METHODS: We examined data collected through a prospective clinical study of HFMD conducted between 2000 and 2006 that included 3 distinct outbreaks of HEV71 to identify risk factors associated with neurological involvement in children with HFMD.
RESULTS: Total duration of fever >or= 3 days, peak temperature >or= 38.5 degrees C and history of lethargy were identified as independent risk factors for neurological involvement (evident by CSF pleocytosis) in the analysis of 725 children admitted during the first phase of the study. When they were validated in the second phase of the study, two or more (>or= 2) risk factors were present in 162 (65%) of 250 children with CSF pleocytosis compared with 56 (30%) of 186 children with no CSF pleocytosis (OR 4.27, 95% CI2.79-6.56, p < 0.0001). The usefulness of the three risk factors in identifying children with CSF pleocytosis on hospital admission during the second phase of the study was also tested. Peak temperature >or= 38.5 degrees C and history of lethargy had the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 28%(48/174), 89%(125/140), 76%(48/63) and 50%(125/251), respectively in predicting CSF pleocytosis in children that were seen within the first 2 days of febrile illness. For those presented on the 3rd or later day of febrile illness, the sensitivity, specificity, PPV and NPV of >or= 2 risk factors predictive of CSF pleocytosis were 75%(57/76), 59%(27/46), 75%(57/76) and 59%(27/46), respectively.
CONCLUSION: Three readily elicited clinical risk factors were identified to help detect children at risk of neurological involvement. These risk factors may serve as a guide to clinicians to decide the need for hospitalization and further investigation, including cerebrospinal fluid examination, and close monitoring for disease progression in children with HFMD.

Matched MeSH terms: Central Nervous System Diseases/etiology*; Central Nervous System Diseases/virology
Fulltext Tuberculous meningitis is a major cause of mortality and morbidity in adults with central nervous system infections in Kota Kinabalu, Sabah, Malaysia: an observational study

Lee HG, William T, Menon J, Ralph AP, Ooi EE, Hou Y, et al.

BMC Infect Dis, 2016 06 16;16:296.
PMID: 27306100 DOI: 10.1186/s12879-016-1640-x

BACKGROUND: Central nervous system (CNS) infections are a significant contributor to morbidity and mortality globally. However, most published studies have been conducted in developed countries where the epidemiology and aetiology differ significantly from less developed areas. Additionally, there may be regional differences due to variation in the socio-economic levels, public health services and vaccination policies. Currently, no prospective studies have been conducted in Sabah, East Malaysia to define the epidemiology and aetiology of CNS infections. A better understanding of these is essential for the development of local guidelines for diagnosis and management.
METHODS: We conducted a prospective observational cohort study in patients aged 12 years and older with suspected central nervous system infections at Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia between February 2012 and March 2013. Cerebrospinal fluid was sent for microscopy, biochemistry, bacterial and mycobacterial cultures, Mycobacterium tuberculosis polymerase chain reaction (PCR), and multiplex and MassCode PCR for various viral and bacterial pathogens.
RESULTS: A total of 84 patients with clinically suspected meningitis and encephalitis were enrolled. An aetiological agent was confirmed in 37/84 (44 %) of the patients. The most common diagnoses were tuberculous meningitis (TBM) (41/84, 48.8 %) and cryptococcal meningoencephalitis (14/84, 16.6 %). Mycobacterium tuberculosis was confirmed in 13/41 (31.7 %) clinically diagnosed TBM patients by cerebrospinal fluid PCR or culture. The acute case fatality rate during hospital admission was 16/84 (19 %) in all patients, 4/43 (9 %) in non-TBM, and 12/41 (29 %) in TBM patients respectively (p = 0.02).
CONCLUSION: TBM is the most common cause of CNS infection in patients aged 12 years or older in Kota Kinabalu, Sabah, Malaysia and is associated with high mortality and morbidity. Further studies are required to improve the management and outcome of TBM.

Matched MeSH terms: Central Nervous System Infections/cerebrospinal fluid; Central Nervous System Infections/microbiology; Central Nervous System Infections/mortality; Central Nervous System Infections/epidemiology
Fulltext Serum concentration of ketamine and antinociceptive effects of ketamine and ketamine-lidocaine infusions in conscious dogs

Kaka U, Saifullah B, Abubakar AA, Goh YM, Fakurazi S, Kaka A, et al.

BMC Vet Res, 2016 Sep 9;12(1):198.
PMID: 27612660

Central sensitization is a potential severe consequence of invasive surgical procedures. It results in postoperative and potentially chronic pain enhancement. It results in postoperative pain enhancement; clinically manifested as hyperalgesia and allodynia. N-methyl-D-aspartate (NMDA) receptor plays a crucial role in the mechanism of central sensitisation. Ketamine is most commonly used NMDA-antagonist in human and veterinary practice. However, the antinociceptive serum concentration of ketamine is not yet properly established in dogs. Six dogs were used in a crossover design, with one week washout period. Treatments consisted of: 1) 0.5 mg/kg ketamine followed by continuous rate infusion (CRI) of 30 μg/kg/min; 2) 0.5 mg/kg ketamine followed by CRI of 30 μg/kg/min and lidocaine (2 mg/kg followed by CRI of 100 μg/kg/min); and 3) 0.5 mg/kg ketamine followed by CRI of 50 μg/kg/min. The infusion was administered up to 120 min. Nociceptive thresholds and ketamine serum concentrations were measured before drug administration, and at 5, 10, 20, 40, 60, 90, 120, 140 and 160 min after the start of infusion.

Matched MeSH terms: Central Nervous System Sensitization
Fulltext Rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD): a case with additional features and review of the literature

Chew HB, Ngu LH, Keng WT

BMJ Case Rep, 2011;2011.
PMID: 22715259 DOI: 10.1136/bcr.02.2010.2706

A rare syndrome of rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) has been recently described. We report the first patient with this syndrome in Southeast Asia and review reported cases to date. Our patient was good health with normal development until the age of 2. He then developed hyperphagic obesity, hypersomnolence, seizures, alveolar hypoventilation, central hypothyroidism, sodium and water dysregulation, gastrointestinal dysmotility, strabismus, disordered temperature and irregular heart rate, altered sweating, delayed puberty, mental retardation and recurrent respiratory tract infections. The cardiomyopathy with heart failure and abnormal cerebral spinal fluid (CSF) neurotransmitter analysis present in our patient have not been reported previously. Tumours of the sympathetic nervous system are known to be associated with this syndrome but had not been found in our patient at the time of reporting. We highlight the difficulty of achieving the diagnosis of ROHHAD syndrome and its overlap with other well-established disease entities. The mortality and morbidity resulting from the high incidence of cardiorespiratory arrest may be prevented by early ventilatory support.

Matched MeSH terms: Autonomic Nervous System Diseases/diagnosis*
Unusual case of cerebral demyelination and bilateral optic neuritis in an infant with suppurative BCG lymphadenitis

Anandakrishnan P, Khoo TB

BMJ Case Rep, 2018 May 30;2018.
PMID: 29848532 DOI: 10.1136/bcr-2018-224496

Cerebral demyelination and optic neuritis are often seen in children with acute disseminated encephalomyelitis following various infections and immunisations. An eight month old girl presented with a left axillary lymph node swelling and an erythematous lace-like rash over her cheeks and trunk. She then developed acute encephalopathy, bilateral nystagmus, right hemiparesis and left facial nerve palsy. Her electroencephalogram showed an encephalopathic process and visual evoked response study were grossly abnormal. Her MRI brain showed hyperintensities in the midbrain, pons and bilateral cerebellar peduncles. She was treated as postinfectious cerebral demyelination with intravenous antibiotics, methylprednisolone and immunoglobulin. Left axillary lymph node excision biopsy and GeneXpert test detected Mycobacterium tuberculosis complex that prompted initiation of antituberculous therapy. Her chest X-ray and cerebrospinal fluid examinations for tuberculosis were normal. She showed significant recovery after 2 weeks. This case illustrates a rare presentation of cerebral demyelination and bilateral optic neuritis following suppurative BCG lymphadenitis.

Matched MeSH terms: Tuberculosis, Central Nervous System/chemically induced
Anterior spinal cord syndrome as a rare complication of acute bacterial meningitis in an adult

Ng KS, Abdul Halim S

BMJ Case Rep, 2018 Oct 24;2018.
PMID: 30361450 DOI: 10.1136/bcr-2018-226082

Acute bacterial meningitis is not an uncommon central nervous system infection. In severe cases, it can be associated with various neurological or systemic complications. However, acute spinal cord dysfunction rarely occurs. We report a case of bacterial meningitis complicated with spinal cord infarction despite adequate treatment with antibiotics and corticosteroid therapy. He had residual paraplegia and was fully dependent in the activity of daily living.

Matched MeSH terms: Central Nervous System Bacterial Infections/diagnosis*; Central Nervous System Bacterial Infections/drug therapy
Autism and trichotillomania in an adolescent boy

Masiran R

BMJ Case Rep, 2018 Sep 05;2018.
PMID: 30185454 DOI: 10.1136/bcr-2018-226270

An adolescent with autism spectrum disorder and improperly treated attention deficit hyperactivity disorder presented with recurrent hair pulling. Treatment with selective serotonin reuptake inhibitor and stimulant improved these conditions.

Matched MeSH terms: Central Nervous System Stimulants/therapeutic use*
Fulltext Bickerstaff brainstem encephalitis with Guillain-Barré syndrome overlap following chlamydia infection

Wong CK, Ng CF, Tan HJ, Mukari SAM

BMJ Case Rep, 2021 May 24;14(5).
PMID: 34031085 DOI: 10.1136/bcr-2021-242090

Bickerstaff brainstem encephalitis (BBE) is a rare autoimmune encephalitis characterised by ataxia, ophthalmoplegia and altered consciousness. An overlap between BBE with Guillain-Barré syndrome (GBS) shows similar clinical and immunological features. We report a case of BBE with GBS overlap secondary to Chlamydia pneumoniae infection. The triad of altered consciousness, ataxia and ophthalmoplegia were present in the patient. The investigations included cerebrospinal fluid cytoalbuminological dissociation, nerve conduction test that showed prolonged or absent F wave latencies, hyperintensity in the left occipital region on brain MRI and diffuse slow activity on the electroencephalogram. The chlamydia serology was positive indicating a postinfectious cause of BBE syndrome. He required artificial ventilation as his consciousness level deteriorated with tetraparesis, oropharyngeal and respiratory muscle weakness. Immunotherapy with intravenous immunoglobulin and methylprednisolone was commenced. He made good recovery with the treatment. Prompt recognition of this rare condition following chlamydia infection is important to guide the management.

Matched MeSH terms: Autoimmune Diseases of the Nervous System*
Fulltext Therapeutic plasma exchange (TPE) for semi-critical neurology presentations in a non-acute neurology set-up: clinical practice and challenges

Fu KS, Wong PY, Hiew FL

BMJ Neurol Open, 2020;2(1):e000020.
PMID: 33681775 DOI: 10.1136/bmjno-2019-000020

Introduction: Therapeutic plasma exchange (TPE) for semi-critical neurological manifestations can be managed in non-acute setting instead of critical care unit. In 2014, we established a non-acute neurology TPE unit for semi-critical haemodynamically stable patients. In this study, we aimed to evaluate the technical and safety parameters from the first 3 years of service.
Materials and methods: We analysed prospectively collected TPE data for patients treated with centrifugation TPE at our non-acute neurology TPE unit in Kuala Lumpur Hospital between May 2015 and June 2018.
Results: A total of 245 TPE procedures were performed in 55 patients for nine neurological indications, predominantly the central nervous system (79%). Twenty four per cent (n=13) had category I and 73% (n=40) had category II indication (American Society for Apheresis (ASFA) 2019). Others (4%) were not in ASFA indications. Neuromyelitis optica spectrum disorders accounted for half (51%) of the total patients. Twenty-three (41.8%) patients experienced adverse events, with hypotensive episodes being the the most common (n=12/55, 21.8%). Five (9.1%) patients had catheter-related blood stream infection, correlating with higher exchange plasma volume (p=0.023). Symptomatic hypocalcaemia was less common (n=5/55, 9.1%) and allergic reaction to human albumin was rare (n=1/55, 1.8%). Four technical errors detected. Three involved centrifugation sets manufacturing defects and one involved error in centrifugation set installation. Seven (2.9%) procedures were terminated: 5 for adverse effects and 2 for technical errors.
Conclusion: Performing TPE among semi-critical patients with neurology manifestations in basic non-acute set-up proved safe, with predictable complications. This set-up reduced the reliance on critical care services for TPE procedures.

Matched MeSH terms: Central Nervous System
Time dependent effect of chronic embryonic exposure to ethanol on zebrafish: Morphology, biochemical and anxiety alterations

Ramlan NF, Sata NSAM, Hassan SN, Bakar NA, Ahmad S, Zulkifli SZ, et al.

Behav Brain Res, 2017 08 14;332:40-49.
PMID: 28559182 DOI: 10.1016/j.bbr.2017.05.048

Exposure to ethanol during critical period of development can cause severe impairments in the central nervous system (CNS). This study was conducted to assess the neurotoxic effects of chronic embryonic exposure to ethanol in the zebrafish, taking into consideration the time dependent effect. Two types of exposure regimen were applied in this study. Withdrawal exposure group received daily exposure starting from gastrulation until hatching, while continuous exposure group received daily exposure from gastrulation until behavioural assessment at 6dpf (days post fertilization). Chronic embryonic exposure to ethanol decreased spontaneous tail coiling at 24hpf (hour post fertilization), heart rate at 48hpf and increased mortality rate at 72hpf. The number of apoptotic cells in the embryos treated with ethanol was significantly increased as compared to the control. We also measured the morphological abnormalities and the most prominent effects can be observed in the treated embryos exposed to 1.50% and 2.00%. The treated embryos showed shorter body length, larger egg yolk, smaller eye diameter and heart edema as compared to the control. Larvae received 0.75% continuous ethanol exposure exhibited decreased swimming activity and increased anxiety related behavior, while withdrawal ethanol exposure showed increased swimming activity and decreased anxiety related behavior as compared to the respective control. Biochemical analysis exhibited that ethanol exposure for both exposure regimens altered proteins, lipids, carbohydrates and nucleic acids of the zebrafish larvae. Our results indicated that time dependent effect of ethanol exposure during development could target the biochemical processes thus leading to induction of apoptosis and neurobehavioral deficits in the zebrafish larvae. Thus it raised our concern about the safe limit of alcohol consumption for pregnant mother especially during critical periods of vulnerability for developing nervous system.

Matched MeSH terms: Central Nervous System Depressants/toxicity*
Fulltext Following "the Roots" of Kratom (Mitragyna speciosa): The Evolution of an Enhancer from a Traditional Use to Increase Work and Productivity in Southeast Asia to a Recreational Psychoactive Drug in Western Countries

Cinosi E, Martinotti G, Simonato P, Singh D, Demetrovics Z, Roman-Urrestarazu A, et al.

Biomed Res Int, 2015;2015:968786.
PMID: 26640804 DOI: 10.1155/2015/968786

The use of substances to enhance human abilities is a constant and cross-cultural feature in the evolution of humanity. Although much has changed over time, the availability on the Internet, often supported by misleading marketing strategies, has made their use even more likely and risky. This paper will explore the case of Mitragyna speciosa Korth. (kratom), a tropical tree used traditionally to combat fatigue and improve work productivity among farm populations in Southeast Asia, which has recently become popular as novel psychoactive substance in Western countries. Specifically, it (i) reviews the state of the art on kratom pharmacology and identification; (ii) provides a comprehensive overview of kratom use cross-culturally; (iii) explores the subjective experiences of users; (iv) identifies potential risks and side-effects related to its consumption. Finally, it concludes that the use of kratom is not negligible, especially for self-medication, and more clinical, pharmacological, and socioanthropological studies as well as a better international collaboration are needed to tackle this marginally explored phenomenon.

Matched MeSH terms: Central Nervous System Stimulants
Fulltext Schiff base metal derivatives enhance the expression of HSP70 and suppress BAX proteins in prevention of acute gastric lesion

Golbabapour S, Gwaram NS, Al-Obaidi MM, Soleimani AF, Ali HM, Abdul Majid N

Biomed Res Int, 2013;2013:703626.
PMID: 24298554 DOI: 10.1155/2013/703626

Schiff base complexes have appeared to be promising in the treatment of different diseases and disorders and have drawn a lot of attention to their biological activities. This study was conducted to evaluate the regulatory effect of Schiff base metal derivatives on the expression of heat shock proteins (HSP) 70 and BAX in protection against acute haemorrhagic gastric ulcer in rats. Rats were assigned to 6 groups of 6 rats: the normal control (Tween 20 5% v/v, 5 mL/kg), the positive control (Tween 20 5% v/v, 5 mL/kg), and four Schiff base derivative groups named Schiff_1, Schiff_2, Schiff_3, and Schiff_4 (25 mg/kg). After 1 h, all of the groups received ethanol 95% (5 mL/kg) but the normal control received Tween 20 (Tween 20 5% v/v, 5 mL/kg). The animals were euthanized after 60 min and the stomachs were dissected for histology (H&E), immunohistochemistry, and western blot analysis against HSP70 and BAX proteins. The results showed that the Schiff base metal derivatives enhanced the expression of HSP70 and suppressed the expression of BAX proteins during their gastroprotection against ethanol-induced gastric lesion in rats.

Matched MeSH terms: Central Nervous System Depressants/adverse effects; Central Nervous System Depressants/pharmacology
Fulltext Antioxidant and hepatoprotective effect of aqueous extract of germinated and fermented mung bean on ethanol-mediated liver damage

Mohd Ali N, Mohd Yusof H, Long K, Yeap SK, Ho WY, Beh BK, et al.

Biomed Res Int, 2013;2013:693613.
PMID: 23484140 DOI: 10.1155/2013/693613

Mung bean is a hepatoprotective agent in dietary supplements. Fermentation and germination processes are well recognized to enhance the nutritional values especially the concentration of active compounds such as amino acids and GABA of various foods. In this study, antioxidant and hepatoprotective effects of freeze-dried mung bean and amino-acid- and GABA-enriched germinated and fermented mung bean aqueous extracts were compared. Liver superoxide dismutase (SOD), malondialdehyde (MDA), ferric reducing antioxidant power (FRAP), nitric oxide (NO) levels, and serum biochemical profile such as aspartate transaminase (AST), alanine transaminase (ALT), triglycerides (TG), and cholesterol and histopathological changes were examined for the antioxidant and hepatoprotective effects of these treatments. Germinated and fermented mung bean have recorded an increase of 27.9 and 7.3 times of GABA and 8.7 and 13.2 times of amino acid improvement, respectively, as compared to normal mung bean. Besides, improvement of antioxidant levels, serum markers, and NO level associated with better histopathological evaluation indicated that these extracts could promote effective recovery from hepatocyte damage. These results suggested that freeze-dried, germinated, and fermented mung bean aqueous extracts enriched with amino acids and GABA possessed better hepatoprotective effect as compared to normal mung bean.

Matched MeSH terms: Central Nervous System Depressants/adverse effects*; Central Nervous System Depressants/pharmacology
Fulltext Review on Cross Talk between Neurotransmitters and Neuroinflammation in Striatum and Cerebellum in the Mediation of Motor Behaviour

Abg Abd Wahab DY, Gau CH, Zakaria R, Muthu Karuppan MK, A-Rahbi BS, Abdullah Z, et al.

Biomed Res Int, 2019;2019:1767203.
PMID: 31815123 DOI: 10.1155/2019/1767203

Neurological diseases particularly Alzheimer's disease (AD), Parkinson's disease (PD), stroke, and epilepsy are on the rise all around the world causing morbidity and mortality globally with a common symptom of gradual loss or impairment of motor behaviour. Striatum, which is a component of the basal ganglia, is involved in facilitating voluntary movement while the cerebellum is involved in the maintenance of balance and coordination of voluntary movements. Dopamine, serotonin, gamma-aminobutyric acid (GABA), and glutamate, to name a few, interact in regulating the excitation and inhibition of motor neurons. In another hand, interestingly, the motor loss associated with neurological diseases is possibly resulted from neuroinflammation induced by the neuroimmune system. Toll-like receptors (TLRs) are present in the central nervous system (CNS), specifically and primarily expressed in microglia and are also found on neurons and astrocytes, functioning mainly in the regulation of proinflammatory cytokine production. TLRs are always found to be associated or involved in the induction of neuroinflammation in neurodegenerative diseases. Activation of toll-like receptor 4 (TLR4) through TLR4 agonist, lipopolysaccharide (LPS), stimulation initiate a signaling cascade whereby the TLR4-LPS interaction has been found to result in physiological and behavioural changes including retardation of motor activity in the mouse model. TLR4 inhibitor TAK-242 was reflected in the reduction of the spinal cord pathology along with the motor improvement in ALS mouse. There is cross talk with neuroinflammation and neurochemicals. For example, TLR4 activation by LPS is noted to release proinflammatory cytokines, IL-1β, from microglia that subsequently suppresses GABA receptor activities at the postsynaptic site and reduces GABA synthesis at the presynaptic site. Glial glutamate transporter activities are also found to be suppressed, showing the association between TLR4 activation and the related neurotransmitters and corresponding receptors and transporters in the event of neuroinflammation. This review is helpful to understand the connection between neurotransmitter and neuroinflammation in striatum- and cerebellum-mediated motor behaviour.

Matched MeSH terms: Central Nervous System/drug effects
Fulltext Mesenchymal Stem Cell-Derived Extracellular Vesicles: Regenerative Potential and Challenges

Fuloria S, Subramaniyan V, Dahiya R, Dahiya S, Sudhakar K, Kumari U, et al.

Biology (Basel), 2021 Feb 25;10(3).
PMID: 33668707 DOI: 10.3390/biology10030172

Evidence suggests that stem cells exert regenerative potential via the release of extracellular vesicles. Mesenchymal stem cell extracellular vesicles (MSCEVs) offer therapeutic benefits for various pathophysiological ailments by restoring tissues. Facts suggest that MSCEV action can be potentiated by modifying the mesenchymal stem cells culturing methodology and bioengineering EVs. Limited clinical trials of MSCEVs have questioned their superiority, culturing quality, production scale-up and isolation, and administration format. Translation of preclinically successful MSCEVs into a clinical platform requires paying attention to several critical matters, such as the production technique, quantification/characterization, pharmacokinetics/targeting/transfer to the target site, and the safety profile. Keeping these issues as a priority, the present review was designed to highlight the challenges in translating preclinical MSCEV research into clinical platforms and provide evidence for the regenerative potential of MSCEVs in various conditions of the liver, kidney, heart, nervous system, bone, muscle, cartilage, and other organs/tissues.

Matched MeSH terms: Nervous System

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