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Fulltext Paraspinal back muscles in asymptomatic volunteers: quantitative and qualitative analysis using computed tomography (CT) and magnetic resonance imaging (MRI)

Khil EK, Choi JA, Hwang E, Sidek S, Choi I

BMC Musculoskelet Disord, 2020 Jun 26;21(1):403.
PMID: 32590960 DOI: 10.1186/s12891-020-03432-w

BACKGROUND: To evaluate paraspinal back muscles of asymptomatic subjects using qualitative and quantitative analysis on CT and MRI and correlate the results with demographic data.
METHODS: Twenty-nine asymptomatic subjects were enrolled prospectively (age: mean 34.31, range 23-50; 14 men, 15 women) from August 2016 to April 2017. Qualitative analysis of muscles was done using Goutallier's system on CT and MRI. Quantitative analysis entailed cross sectional area (CSA) on CT and MRI, Hounsfield unit (HU) on CT, fat fraction using two-point Dixon technique on MRI. Three readers independently analyzed the images; intra- and inter-observer agreements were measured. Linear regression and Spearman's analyses were used for correlation with demographic data.
RESULTS: CSA values were significantly higher in men (p

Matched MeSH terms: Muscular Atrophy/pathology; Muscular Atrophy/physiopathology; Paraspinal Muscles/pathology*; Paraspinal Muscles/physiopathology
Rutin loaded liquid crystalline nanoparticles inhibit non-small cell lung cancer proliferation and migration in vitro

Paudel KR, Wadhwa R, Tew XN, Lau NJX, Madheswaran T, Panneerselvam J, et al.

Life Sci, 2021 Jul 01;276:119436.
PMID: 33789146 DOI: 10.1016/j.lfs.2021.119436

Non-small cell lung cancer (NSCLC) is one of the major causes of cancer-related mortality globally. Despite the availability of therapeutic options, the improvement in patient survival is yet to be achieved. Recent advances in natural product (e.g., Rutin) research, therapeutic nanotechnology and especially the combination of both could aid in achieving significant improvements in the treatment or management of NSCLC. In this study, we explore the anti-cancer activity of Rutin-loaded liquid crystalline nanoparticles (LCNs) in an in vitro model where we have employed the A549 human lung epithelial carcinoma cell line. The anti-proliferative activity was determined by MTT and Trypan blue assays, whereas, the anti-migratory activity was evaluated by the scratch wound healing assay and a modified Boyden chamber assay. We also evaluated the anti-apoptotic activity by Annexin V-FITC staining, and the colony formation activity was studied using crystal violet staining. Here, we report that Rutin-LCNs showed promising anti-proliferative and anti-migratory activities. Furthermore, Rutin-LCNs also induced apoptosis in the A549 cells and inhibited colony formation. The findings warrant further detailed and in-depth anti-cancer mechanistic studies of Rutin-LCNs with a focus towards a potential therapeutic option for NSCLC. LCNs may help to enhance the solubility of Rutin used in the treatment of lung cancer and hence enhance the anticancer effect of Rutin.

Matched MeSH terms: Carcinoma, Non-Small-Cell Lung/pathology; Lung Neoplasms/pathology
Fulltext A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank

Shen X, Howard DM, Adams MJ, Hill WD, Clarke TK, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, et al.

Nat Commun, 2020 05 08;11(1):2301.
PMID: 32385265 DOI: 10.1038/s41467-020-16022-0

Depression is a leading cause of worldwide disability but there remains considerable uncertainty regarding its neural and behavioural associations. Here, using non-overlapping Psychiatric Genomics Consortium (PGC) datasets as a reference, we estimate polygenic risk scores for depression (depression-PRS) in a discovery (N = 10,674) and replication (N = 11,214) imaging sample from UK Biobank. We report 77 traits that are significantly associated with depression-PRS, in both discovery and replication analyses. Mendelian Randomisation analysis supports a potential causal effect of liability to depression on brain white matter microstructure (β: 0.125 to 0.868, pFDR

Matched MeSH terms: Depression/pathology; Prefrontal Cortex/pathology
Improved functional assessment of osteoarthritic knee joint after chondrogenically induced cell treatment

Ude CC, Ng MH, Chen CH, Htwe O, Amaramalar NS, Hassan S, et al.

Osteoarthritis Cartilage, 2015 Aug;23(8):1294-306.
PMID: 25887366 DOI: 10.1016/j.joca.2015.04.003

OBJECTIVES: Our previous studies on osteoarthritis (OA) revealed positive outcome after chondrogenically induced cells treatment. Presently, the functional improvements of these treated OA knee joints were quantified followed by evaluation of the mechanical properties of the engineered cartilages.
METHODS: Baseline electromyogram (EMGs) were conducted at week 0 (pre-OA), on the locomotory muscles of nine un-castrated male sheep (Siamese long tail cross) divided into controls, adipose-derived stem cells (ADSCs) and bone marrow stem cells (BMSCs), before OA inductions. Subsequent recordings were performed at week 7 and week 31 which were post-OA and post-treatments. Afterwards, the compression tests of the regenerated cartilage were performed.
RESULTS: Post-treatment EMG analysis revealed that the control sheep retained significant reductions in amplitudes at the right medial gluteus, vastus lateralis and bicep femoris, whereas BMSCs and ADSCs samples had no further significant reductions (P < 0.05). Grossly and histologically, the treated knee joints demonstrated the presence of regenerated neo cartilages evidenced by the fluorescence of PKH26 tracker. Based on the International Cartilage Repair Society scores (ICRS), they had significantly lower grades than the controls (P < 0.05). The compression moduli of the native cartilages and the engineered cartilages differed significantly at the tibia plateau, patella femoral groove and the patella; whereas at the medial femoral condyle, they had similar moduli of 0.69 MPa and 0.40-0.64 MPa respectively. Their compression strengths at all four regions were within ±10 MPa.
CONCLUSION: The tissue engineered cartilages provided evidence of functional recoveries associated to the structural regenerations, and their mechanical properties were comparable with the native cartilage.
KEYWORDS: Cartilage; Cell therapy; Function; Osteoarthritis; Regeneration

Matched MeSH terms: Arthritis, Experimental/physiopathology; Cartilage, Articular/pathology; Cartilage, Articular/physiopathology; Osteoarthritis/physiopathology; Stifle/pathology; Stifle/physiopathology
Fulltext Philanthotoxin-343 attenuates retinal and optic nerve injury, and protects visual function in rats with N-methyl-D-aspartate-induced excitotoxicity

Fazel MF, Abu IF, Mohamad MHN, Agarwal R, Iezhitsa I, Bakar NS, et al.

PLoS One, 2020;15(7):e0236450.
PMID: 32706792 DOI: 10.1371/journal.pone.0236450

Retinal ganglion cell (RGC) loss and optic neuropathy, both hallmarks of glaucoma, have been shown to involve N-methyl-D-aspartate receptor (NMDAR)-mediated excitotoxicity. This study investigated the neuroprotective effects of Philanthotoxin (PhTX)-343 in NMDA-induced retinal injury to alleviate ensuing visual impairments. Sprague-Dawley rats were divided into three; Group I was intravitreally injected with phosphate buffer saline as the control, Group II was injected with NMDA (160 nM) to induce retinal excitotoxic injury, while Group III was injected with PhTX-343 (160 nM) 24 h prior to excitotoxicity induction with NMDA. Rats were subjected to visual behaviour tests seven days post-treatment and subsequently euthanized. Rat retinas and optic nerves were subjected to H&E and toluidine blue staining, respectively. Histological assessments showed that NMDA exposure resulted in significant loss of retinal cell nuclei and thinning of ganglion cell layer (GCL). PhTX-343 pre-treatment prevented NMDA-induced changes where the RGC layer morphology is similar to the control. The numbers of nuclei in the NMDA group were markedly lower compared to the control (p<0.05). PhTX-343 group had significantly higher numbers of nuclei within 100 μm length and 100 μm2 area of GCL (2.9- and 1.7-fold, respectively) compared to NMDA group (p<0.05). PhTX-343 group also displayed lesser optic nerve fibres degeneration compared to NMDA group which showed vacuolation in all sections. In the visual behaviour test, the NMDA group recorded higher total distance travelled, and lower total immobile time and episodes compared to the control and PhTX-343 groups (p<0.05). Object recognition tests showed that the rats in PhTX-343 group could recognize objects better, whereas the same objects were identified as novel by NMDA rats despite multiple exposures (p<0.05). Visual performances in the PhTX-343 group were all comparable with the control (p>0.05). These findings suggested that PhTX-343 inhibit retinal cell loss, optic nerve damage, and visual impairments in NMDA-induced rats.

Matched MeSH terms: Optic Nerve/pathology; Retinal Ganglion Cells/pathology
Fulltext Anti-Uterine Fibroid Effect of Standardized Labisia Pumila Var. Alata Extracts In Vitro and in Human Uterine Fibroid Cancer Xenograft Model

Zakaria N, Mohd KS, Ahmed Saeed MA, Ahmed Hassan LE, Shafaei A, Al-Suede FSR, et al.

Asian Pac J Cancer Prev, 2020 Apr 01;21(4):943-951.
PMID: 32334454 DOI: 10.31557/APJCP.2020.21.4.943

BACKGROUND: Uterine fibroids are a common type of solid tumor presenting in women of reproductive age. There are very few alternative treatment available from conventional treatment involving surgeries. Labisia pumila var. alata or locally known as 'Kacip Fatimah' was widely used as traditional medicine in Malaysia. This plant has been used to maintain a healthy female reproductive system. The present study aimed to evaluate anti fibroid potential of L. pumila extracts through in vitro apoptosis activity against uterine leiomyoma cells (SK-UT-1) and in uterine leiomyoma xenograft model. Evaluation of bioactive markers content were also carried out.
METHODS: Apoptotic induction of the extracts was determined by morphological examination of AO/PI dual staining assay by flourescent microscopy and flow cytometry analysis on Annexin V-FITC/PI stained cells. In vivo study was done in immune-compromised mouse xenograft model. HPLC analysis was employed to quantify marker compounds.
RESULTS: Morphological analysis showed L. pumila induced apoptosis in a dose dependent manner against SK-UT-1 cells. In vivo study indicated that L. pumila significantly suppressed the growth of uterine fibroid tumor. All tested extracts contain bioactive marker of gallic acid and cafeic acid.
CONCLUSION: This work provide significant data of the potential of L. pumila in management of uterine fibroids.
.

Matched MeSH terms: Leiomyoma/pathology; Uterine Neoplasms/pathology
Variation in BCL2 protein expression in follicular lymphomas without t(14;18) chromosomal translocations

Masir N, Jones M, Abdul-Rahman F, Florence CS, Mason DY

Pathology, 2012 Apr;44(3):228-33.
PMID: 22406486 DOI: 10.1097/PAT.0b013e3283513fb2

The hallmark of follicular lymphoma is the t(14;18)(q32;q21) chromosomal translocations that lead to deregulation of BCL2 expression in tumour cells. However, not all cases of follicular lymphoma express BCL2, nor is the t(14;18) translocation always present. Follicular lymphomas lacking the BCL2 rearrangement are less well studied with regards to their immunohistochemical and molecular features. This study aims to investigate the BCL2 protein expression pattern in t(14;18) negative follicular lymphomas.

Matched MeSH terms: Lymphoma, Follicular/pathology; Trisomy/pathology
Expression of placental proteins in complete and partial hydatidiform moles

Cheah PL, Looi LM

Pathology, 1994 Apr;26(2):115-8.
PMID: 8090580

Examination of routinely stained haematoxylin and eosin sections may sometimes prove inadequate in differentiating partial hydatidiform moles (PHM) from complete hydatidiform moles (CHM). While cytogenetic analysis can aid in the distinction, such facilities are not always available. The possibility of using immunohistochemistry to aid in the differentiation was studied. Twenty-five histologically proven CHM and 11 PHM were studied for their patterns of expression of human chorionic gonadotrophin (hCG), human placental lactogen (hPL) and placental alkaline phosphatase (PIAP). All CHM stained diffusely with hCG and focally with both hPL and PIAP irrespective of gestational age. Of PHM, 63.6% were diffusely positive for hCG, 27.3% for hPL and 54.5% for PIAP; the rest were focally positive. The hCG pattern changed from diffuse to focal with increasing gestational age of PHM, while those of hPL and PIAP became increasingly diffuse with gestational age. While these protein expressions may be applied in differentiating late PHM from CHM, it is not useful in first trimester cases. The most helpful application is that focal expression of hCG and diffuse expressions of hPL and PIAP is not seen in CHM, thereby excluding such a diagnosis. PHM, in contrast, can show either diffuse or focal expression of all 3 antigens.

Matched MeSH terms: Hydatidiform Mole/pathology; Uterine Neoplasms/pathology
The morphology of corneal endothelial cells in long term soft contact lens wearers in Kuala Lumpur

Mohd-Ali B, Chen LY

Cont Lens Anterior Eye, 2021 02;44(1):72-75.
PMID: 32624364 DOI: 10.1016/j.clae.2020.06.007

PURPOSE: To analyse and compare the alterations in corneal endothelium morphology induced by different materials and durations of wearing soft contact lenses (CL) among young adults living in Kuala Lumpur.
METHODS: Healthy soft CL wearers were invited to participate in this study. Visual acuity (VA) was measured using the Snellen chart, and subjective refraction was performed using cross-cylinder technique. Standard ocular assessments were conducted using a slit lamp biomicroscope and morphology of corneal endothelial cells (endothelial cell density, ECD, coefficient variation, COV, hexagonality, HEX and central corneal thickness, CCT) were evaluated using a non-contact specular microscope. Statistical analysis was conducted using ANOVA and data from the right eye only is included.
RESULTS: A total of 72 subjects (32 SiHy and 40 HCL wearers) and 24 non-CL wearers (control) participated in this study. The gender distribution for study subjects was 13 males and 59 females, with a mean age 22.15 ± 1.84 years old. The mean refraction was -1.86 ± 1.25DS. The duration of wearing CL ranged from 1 to 9 years. Subjects were later divided into 2 groups following duration of CL wear: Group 1 (<5 years) and Group 2 (≥5 years) for analysis purposes. Statistical analysis showed significant alterations in ECD, COV and HEX of CL wearers (p

Matched MeSH terms: Endothelium, Corneal/pathology*; Endothelial Cells/pathology
Fulltext An Improved Nanoemulsion Formulation Containing Kojic Monooleate: Optimization, Characterization and In Vitro Studies

Roselan MA, Ashari SE, Faujan NH, Mohd Faudzi SM, Mohamad R

Molecules, 2020 Jun 04;25(11).
PMID: 32512808 DOI: 10.3390/molecules25112616

Tyrosinase inhibitors have become increasingly important targets for hyperpigmentation disease treatment. Kojic monooleate (KMO), synthesized from the esterification of kojic acid and oleic acid, has shown a better depigmenting effect than kojic acid. In this study, the process parameters include the speed of high shear, the time of high shear and the speed of the stirrer in the production of nanoemulsion containing KMO was optimized using Response Surface Methodology (RSM), as well as evaluated in terms of its physicochemical properties, safety and efficacy. The optimized condition for the formulation of KMO nanoemulsion was 8.04 min (time of high shear), 4905.42 rpm (speed of high shear), and 271.77 rpm (speed of stirrer), which resulted in a droplet size of 103.97 nm. An analysis of variance (ANOVA) showed that the fitness of the quadratic polynomial fit the experimental data with large F-values (148.79) and small p-values (p < 0.0001) and an insignificant lack of fit. The optimized nanoemulsion containing KMO with a pH value of 5.75, showed a high conductivity value (3.98 mS/cm), which indicated that the nanoemulsion containing KMO was identified as an oil-in-water type of nanoemulsion. The nanoemulsion remains stable (no phase separation) under a centrifugation test and displays accelerated stability during storage at 4, 25 and 45 °C over 90 days. The cytotoxicity assay showed that the optimized nanoemulsion was less toxic, with a 50% inhibition of cell viability (IC50) > 500 μg/mL, and that it can inhibit 67.12% of tyrosinase activity. This study reveals that KMO is a promising candidate for the development of a safe cosmetic agent to prevent hyperpigmentation.

Matched MeSH terms: Embryo, Mammalian/pathology; Fibroblasts/pathology
Over-expression of MAGED4B increases cell migration and growth in oral squamous cell carcinoma and is associated with poor disease outcome

Chong CE, Lim KP, Gan CP, Marsh CA, Zain RB, Abraham MT, et al.

Cancer Lett, 2012 Aug 1;321(1):18-26.
PMID: 22459352 DOI: 10.1016/j.canlet.2012.03.025

MAGE proteins have been shown to be good targets for cancer immunotherapy. We demonstrate that MAGED4B is over-expressed in more than 50% of Oral Squamous Cell Carcinoma (OSCC) tissues and the expression of MAGED4B is associated with lymph node metastasis and poor disease specific survival. OSCC cell lines that over-express MAGED4B promote migration in vitro, exhibit an increase in cell growth both in vitro and in vivo, and are more resistant to apoptosis compared to control cells. Our data suggest that MAGED4B over-expression is a driver in oral carcinogenesis and argues strongly that this protein may represent a potential therapeutic target in OSCC.

Matched MeSH terms: Carcinoma, Squamous Cell/pathology*; Mouth Neoplasms/pathology*
The Fabry disease-causing mutation, GLA IVS4+919G>A, originated in Mainland China more than 800 years ago

Liang KH, Lu YH, Niu CW, Chang SK, Chen YR, Cheng CY, et al.

J Hum Genet, 2020 Jul;65(7):619-625.
PMID: 32246049 DOI: 10.1038/s10038-020-0745-7

The Fabry disease-causing mutation, the GLA IVS4+919G>A (designated GLA IVS4), is very prevalent in patients with hypertrophic cardiomyopathy in Taiwan. This X-linked mutation has also been found in patients in Kyushu, Japan and Southeast Asia. To investigate the age and the possible ancestral origin of this mutation, a total of 33 male patients with the GLA IVS4+919G>A mutation, born in Taiwan, Japan, Singapore, Malaysia, Vietnam, and the Fujian and Guangdong provinces of China, were studied. Peripheral bloods were collected, and the Ilumina Infinium CoreExome-24 microarray was used for dense genotyping. A mutation-carrying haplotype was discovered which was shared by all 33 patients. This haplotype does not exist in 15 healthy persons without the mutation. Rather, a wide diversity of haplotypes was found in the vicinity of the mutation site, supporting the existence of a single founder of the GLA IVS4 mutation. The age of the founder mutation was estimated by the lengths of the mutation-carrying haplotypes based on the linkage-disequilibrium decay theory. The first, second, and third quartile of the age estimates are 800.7, 922.6, and 1068.4 years, respectively. We concluded that the GLA IVS4+919G>A mutation originated from a single mutational event that occurred in a Chinese chromosome more than 800 years ago.

Matched MeSH terms: Fabry Disease/pathology; Cardiomyopathy, Hypertrophic, Familial/pathology
Drug-induced urticaria and angioedema: pathomechanisms and frequencies in a developing country and in developed countries

Greaves MW, Hussein SH

Int Arch Allergy Immunol, 2002 May;128(1):1-7.
PMID: 12037395 DOI: 10.1159/000057997

A careful drug history should be obtained from all patients with acute or chronic urticaria/angioedema, especially in the elderly. Although strictly comparable data are lacking, drug-induced urticaria appears to be more common in developed countries than in Malaysia, at least in a Hospital setting. Culprit drugs include antibiotics, analgesics and contrast media. Pseudoallergic drug-induced urticaria mimicks true allergic urticaria, but without an evident immunological basis, and is at least as common as the allergic type. In Malaysia, and in many other countries compulsory, ingredient labelling of 'traditional' medicines would do much to reduce the frequency of drug-induced urticaria.

Matched MeSH terms: Angioedema/pathology; Urticaria/pathology
Hyperandrogenism caused by ovarian Leydig cell tumour: finding the needle in a haystack

Tong CV, Tai YT

BMJ Case Rep, 2020 Dec 13;13(12).
PMID: 33318251 DOI: 10.1136/bcr-2020-238012

Leydig cell tumours (LCTs) of the ovary are rare ovarian tumours that usually present with hyperandrogenism. Conventional radiological imagings are helpful in localising these tumours. However, some tumours may be too small to be localised before curative surgical removal. It is important to identify these androgen-secreting neoplasms which originate mostly from adrenals or ovaries because they are potentially malignant and require specific treatment. When conventional imagings are unrevealing, selective ovarian and adrenal venous sampling (SOAVS) is the next option. We report a case of LCT that was localised by SOAVS after results from other imaging modalities remained inconclusive.

Matched MeSH terms: Leydig Cell Tumor/pathology*; Ovarian Neoplasms/pathology*
Fulltext The Role of Piper sarmentosum Aqueous Extract as a Bone Protective Agent, a Histomorphometric Study

Mohamad Asri SF, Soelaiman IN, Mohd Moklas MA, Mohd Nor NH, Mohamad Zainal NH, Mohd Ramli ES

Int J Mol Sci, 2020 Oct 19;21(20).
PMID: 33086468 DOI: 10.3390/ijms21207715

Glucocorticoids are one of the causes of secondary osteoporosis. The aqueous extract of Piper sarmentosum contains flavonoids that possess antioxidant effects. In this study, we determined the effects of aqueous Piper sarmentosum leaf extract on structural, dynamic and static histomorphometric changes from osteoporotic bones of rats induced with glucocorticoids. Thirty-two Sprague-Dawley rats were divided equally into four groups-Sham control group given vehicles (intramuscular (IM) olive oil and oral normal saline); AC: Adrenalectomised (Adrx) control group given IM dexamethasone (DEX) (120 μg/kg/day) and vehicle (oral normal saline); AP: Adrx group administered IM DEX (120 μg/kg/day) and aqueous Piper sarmentosum leaf extract (125 mg/kg/day) orally; and AG: Adrx group administered IM DEX (120 μg/kg/day) and oral glycyrrhizic acid (GCA) (120 mg/kg/day). Histomorphometric measurements showed that the bone volume, trabecular thickness, trabecular number, osteoid and osteoblast surfaces, double-labelled trabecular surface, mineralizing surface and bone formation rate of rats given aqueous Piper sarmentosum leaf extract were significantly increased (p < 0.05), whereas the trabecular separation and osteoclast surface were significantly reduced (p < 0.05). This study suggests that aqueous Piper sarmentosum leaf extract was able to prevent bone loss in prolonged glucocorticoid therapy. Thus, Piper sarmentosum has the potential to be used as an alternative medicine against osteoporosis and osteoporotic fractures in patients undergoing long-term glucocorticoid therapy.

Matched MeSH terms: Bone and Bones/pathology*; Cancellous Bone/pathology
Fulltext The frequency of pulmonary hypertension in newborn with intrauterine growth restriction

Abbas G, Shah S, Hanif M, Shah A, Rehman AU, Tahir S, et al.

Sci Rep, 2020 05 15;10(1):8064.
PMID: 32415157 DOI: 10.1038/s41598-020-65065-2

Intrauterine growth restriction (IUGR) is a clinical definition applied to neonates born with clinical features of malnutrition and in-utero growth retardation irrespective of their birth weight percentile. This study was aimed to determine the frequency of pulmonary hypertension (PH) in neonates with IUGR. In this descriptive cross-sectional study, we followed 96 neonates with IUGR (≤28 days) and 38 neonates without IUGR born in the department of the neonatal intensive care unit children hospital complex Multan, Pakistan. We analyzed certain factors such as gender, gestational age (GA) (weeks), birth weight (BW in kg), weight percentile (WP) for GA, meconium aspiration syndrome (MAS), birth asphyxia (BA) and respiratory distress syndrome (RDS) for pulmonary hypertension (PH) in IUGR and non-IUGR group. GA was measured by the Ballard scoring system. Echocardiography was performed for all patients by the pediatric cardiologist to measure pulmonary arterial (PA) pressure using Bernoulli's equation. Out of total 96 IUGR neonates, 33.3% (n = 32) suffered from PH, of which 65.3% (n = 18) were male and 43.7% (n = 14) were female. The percentages of IUGR neonates with BA, MAS and RDS were 34.4%, 18.8% and 22.9% respectively. The data were analyzed using the SPSS-16 software to test the statistical significance of the results. A p-value less than 0.05 was considered significant. When the chi-square test was applied, it depicted that MAS was significantly associated with PH in IUGR neonates (p = 0.0001) compared to non-IUGR neonates. Our findings suggested an increased chance of PH in IUGR neonates and MAS may be a strong factor.

Matched MeSH terms: Fetal Growth Retardation/physiopathology*; Hypertension, Pulmonary/pathology; Infant, Premature, Diseases/pathology
Antifungal prophylaxis in lung transplantation

Neoh CF, Snell G, Levvey B, Morrissey CO, Stewart K, Kong DC

Int J Antimicrob Agents, 2014 Sep;44(3):194-202.
PMID: 25123811 DOI: 10.1016/j.ijantimicag.2014.05.013

Lung transplant (LTx) patients have an increased risk of developing invasive fungal infections (IFIs), particularly invasive aspergillosis. Rapid identification of the causative fungal pathogen, to allow for early administration of appropriate initial antifungal therapy, in LTx patients has been challenging due to the limited sensitivity and specificity of the diagnostic tools. Hence, there is increasing emphasis on antifungal prophylaxis in the LTx setting, given the high mortality rates and substantial cost of treating IFIs. Evidence for the optimal antifungal prophylactic approach in this setting, however, remains scant and inconsistent. This review will briefly discuss the epidemiology, risk factors, timing and clinical manifestations of fungal infections in LTx patients and will focus primarily on the available evidence related to the efficacy, safety and practicality of current prophylactic strategies in LTx recipients as well as challenges and gaps for future research.

Matched MeSH terms: Mycoses/pathology; Opportunistic Infections/pathology
Orlistat reverses intratesticular lactate transport decline and infertility in male obese rats

Suleiman JB, Nna VU, Zakaria Z, Othman ZA, Bakar ABA, Usman UZ, et al.

Reproduction, 2020 12;160(6):863-872.
PMID: 33112813 DOI: 10.1530/REP-20-0381

Obesity and its accompanying complications predispose to abnormal testicular glucose metabolism, penile erectile dysfunction and subfertility. This study examined the potentials of orlistat in attenuating erectile dysfunction and fertility decline in high-fat diet (HFD)-induced obesity in male rats. Eighteen adult male Sprague-Dawley rats whose weights were between 250 and 300 g were divided into three groups (n = 6/group) namely: normal control (NC), HFD and HFD + orlistat (10 mg/kg body weight/day co-administered for 12 weeks) (HFD+O). During the 11th and 12th week, mating behaviour and fertility parameters were evaluated, and parameters of glucose metabolism were assessed at the end of the 12th week. Orlistat increased testicular mRNA levels of glucose transporters (Glut1 and Glut3), monocarboxylate transporters (Mct2 and Mct4) and lactate dehydrogenase type C (Ldhc), decreased intratesticular lactate and glucose levels, and LDH activity in obese rats. Furthermore, orlistat increased superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) activities, and total antioxidant capacity (TAC), but decreased malondialdehyde level in the penis of obese rats. Similarly, orlistat improved penile cGMP level, sexual behaviour and fertility outcome in obese rats. Penile cGMP level correlated positively with total mounts and intromissions but correlated negatively with mount/intromission ratio. Orlistat improves fertility potential in obese state by targeting testicular lactate metabolism, penile oxidative stress and sexual behaviour in rats. Therefore, orlistat shows a promising protective effect and may preserve the fertility potential of obese men.

Matched MeSH terms: Infertility, Male/pathology; Obesity/pathology
Resistance against tumour necrosis factor α apoptosis by the cellular prion protein is cell-specific for oral, colon and kidney cancer cell lines

Yap YH, Say YH

Cell Biol Int, 2012 Mar 1;36(3):273-7.
PMID: 21980981 DOI: 10.1042/CBI20110088

Since the discovery of PrPC (cellular prion protein), most studies have focused on its role in neurodegenerative diseases, whereas its function outside the nervous system remains obscure. We investigated the ability of PrPC in resisting TNFα (tumour necrosis factor α) apoptosis in three PrPC-transiently transfected cancer cell lines, renal adenocarcinoma ACHN, oral squamous cell carcinoma HSC-2 and colon adenocarcinoma LS174T. PrPC-expressing ACHN and LS174T cells had higher viabilities compared with the mock-transfected cells, while the transient overexpression of PrPC had minimal overall effect on HSC-2 cells due to its high endogenous PrPC expression. Cell cycles were also analysed, with both PrPC expressing ACHN and LS174T cells having a significantly higher proliferative index than mock-transfected cells. Flow cytometry analysis indicated a G1/S-phase cell cycle transition in both PrPC-expressing ACHN and LS174T cells. PrPC resists TNFα apoptosis due to a modest, but statistically significant, cell-specific cytoprotection compared with mock-transfected cells.

Matched MeSH terms: Carcinoma, Renal Cell/pathology; Colon/pathology
Fulltext Postoperative intraspinal subdural collections after pediatric posterior fossa tumor resection: incidence, imaging, and clinical features

Harreld JH, Mohammed N, Goldsberry G, Li X, Li Y, Boop F, et al.

AJNR Am J Neuroradiol, 2015 May;36(5):993-9.
PMID: 25614472 DOI: 10.3174/ajnr.A4221

Postoperative intraspinal subdural collections in children after posterior fossa tumor resection may temporarily hinder metastasis detection by MR imaging or CSF analysis, potentially impacting therapy. We investigated the incidence, imaging and clinical features, predisposing factors, and time course of these collections after posterior fossa tumor resection.

Matched MeSH terms: Spinal Cord/pathology*; Spinal Cord Diseases/pathology

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