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Fulltext Endocannabinoid system and cardio-metabolic risk

Loh KY, Kew ST

Med J Malaysia, 2008 Oct;63(4):348-50; quiz 351.
PMID: 19385504 MyJurnal

Recent research in bio-medical science has shown an integral role of endocannabinoid system (ECS) in determining cardio-metabolic risk of human body. The mechanism is mediated through binding of endocannabinoids at the CB1 receptors. The stimulation of CB1 receptor in the brain is believed to control and mediate the effects on appetite. In normal physiology, CB1 receptors activation is responsible for energy homeostasis, govern emotions and behaviors such as anxiety, fear, appetite, food and water intake. CB1 receptors also found in peripheral tissues like liver, pancreas, skeletal muscles and adipose tissues, which play an important role in lipid and glucose metabolism. Over-activation of ECS is associated with various metabolic diseases such as dyslipidemia, insulin resistance, lipogenesis, excessive weight gain and increasing intra-abdominal obesity. All these events lead to increased cardiovascular risk. Use of selective CB1 receptor blocker such as rimonabant has shown to reduced waist circumference, better glycemic control, lower triglyceride levels, raise HDL cholesterol and over all reduction in total body fat. This drug has been recommended for patients with metabolic syndrome.

Matched MeSH terms: Piperidines/therapeutic use
Efficacy and safety of topical Trikatu preparation in, relieving mosquito bite reactions: a randomized controlled trial

Maenthaisong R, Chaiyakunapruk N, Tiyaboonchai W, Tawatsin A, Rojanawiwat A, Thavara U

Complement Ther Med, 2014 Feb;22(1):34-9.
PMID: 24559814 DOI: 10.1016/j.ctim.2013.08.014

INTRODUCTION: Trikatu is composed of dried fruits of Piper nigrum L and Piper retrofractum Vahl, and dried rhizomes of Zingiber officinale R. Although this preparation has been used to relieve pruritis, pain, and inflammation for a long time, there is no clinical evidence to confirm its efficacy and safety. Therefore, we performed a double-blind, within person-randomized controlled study of 30 healthy volunteers to determine efficacy and safety of topical Trikatu on mosquito bite reactions.
METHODS: All subjects were bitten by Aedes aegypti laboratory mosquitoes on their forearms and they were randomly assigned arms to apply either Trikatu or reference product on the mosquito bite papule. The main outcome was the difference of papule size reduction at 30 min, measured by a caliper, between the Trikatu and reference arms. Pruritis, redness, pain, and patient satisfaction were assessed at 15, 30, 60, 180, and 360 min as secondary outcomes.
RESULTS: There were no significant differences between treatment and reference arms on any outcome at any time of measurement.
CONCLUSION: Trikatu did not show additional effects for relieving mosquito bite reaction as compared with the reference product containing camphor, menthol, and eucalyptus. For further study, it is very important to consider a proper selection of subjects, comparator product, and concentration of extract when Trikatu preparation is investigated.
KEYWORDS: Eucalyptus oil; Mosquito bite; Mosquito bite symptoms; Papule size reduction; Trikatu preparation

Matched MeSH terms: Piperidines/therapeutic use*
Pisa syndrome secondary to rivastigmine: a case report

Muthupalaniappen L, Rosdinom R, Suguna M

Clin Ter, 2012;163(1):31-2.
PMID: 22362231

Pisa syndrome or pleurothotonus is the persistent flexion of the body and head to one side giving the appearance of the leaning tower of Pisa. It is most commonly caused by typical and atypical antipsychotic drugs. We report a case of Pisa Syndrome caused by prolonged use of high dose cholinesterase inhibitor, rivastigmine. Symptoms subsided when rivastigmine was withdrawn and did not reappear when a different cholinesterase inhibitor, donepezil was introduced. Physicians should be aware of Pisa syndrome and should alert patient of this possibility when starting and stepping up medications. The purpose of reporting this case is to create awareness among general practitioners as it is a reversible condition which responds to removal of the offending drug.

Matched MeSH terms: Piperidines/therapeutic use
Fulltext An open label comparative study of glimepiride versus repaglinide in type 2 diabetes mellitus Muslim subjects during the month of Ramadan

Anwar A, Azmi KN, Hamidon BB, Khalid BA

Med J Malaysia, 2006 Mar;61(1):28-35.
PMID: 16708731 MyJurnal

This study was conducted to compare the treatment efficacy between a prandial glucose regulator, repaglinide and a new sulphonylurea, glimepiride in Muslim Type 2 diabetic patients who practice Ramadan fasting. Forty-one patients, previously treated with a sulphonylurea or metformin, were divided to receive either repaglinide (n=20, preprandially three-times daily) or glimepiride (n=21, preprandially once daily) 3 months before the month of Ramadan. During Ramadan, patients modified their eating pattern to two meals daily, and the triple doses of repaglinide were redistributed to two preprandial doses. Four point blood glucose monitoring were performed weekly during the month of Ramadan and the subsequent month. Measurements of the 4-point blood glucose were significantly lower in the glimepiride group compared to the repaglinide group both during and after Ramadan. The glycaemic excursion was better in the morning for the repaglinide group and better in the afternoon and evening for the glimepiride group during the Ramadan period. There was no statistically significant difference in the incidence of hypoglycaemia between the two groups during and after Ramadan. There was no difference in the glycaemic excursion post-Ramadan. The longer duration of action of glimepiride may offer an advantage over repaglinide during the 13.5 hours of fast in Ramadan for diabetic patients.

Matched MeSH terms: Piperidines/therapeutic use*
Repaglinide versus glibenclamide treatment of Type 2 diabetes during Ramadan fasting

Mafauzy M

Diabetes Res Clin Pract, 2002 Oct;58(1):45-53.
PMID: 12161056 DOI: 10.1016/s0168-8227(02)00104-3

This study compared treatment with a prandial glucose regulator (repaglinide) and a sulphonylurea (glibenclamide) in Muslim Type 2 diabetic patients who practice Ramadan fasting. Two hundred and thirty-five patients, previously treated with a sulphonylurea, were randomised to receive either repaglinide (n=116, preprandially three-times daily) or glibenclamide (n=119, preprandially once- or twice-daily) 6 weeks before Ramadan. During Ramadan, patients changed their eating pattern to two meals daily, and the daily dose of repaglinide was redistributed to two preprandial doses. After Ramadan, patients resumed their regular meal pattern and treatment dosage for 4 weeks. During Ramadan, a statistically significant reduction in mean serum fructosamine concentration from baseline was observed in the repaglinide group (-16.9+/-4.9 micromol/l, -3.8%, P<0.05) but not the glibenclamide group (-6.9+/-4.8 micromol/l, -0.8%). Difference in change in HbA(1c) from baseline was not statistically significant between groups. The number of hypoglycaemic events with midday blood glucose <4.5 mmol/l was significantly lower in the repaglinide group (2.8%) than the glibenclamide group (7.9%) (P=0.001). Apart from hypoglycaemia, both treatments were equally well tolerated. Type 2 diabetic Muslims using prandial repaglinide showed a trend towards better glycaemic control and had a lower frequency of hypoglycaemia than patients using glibenclamide during Ramadan.

Matched MeSH terms: Piperidines/therapeutic use*
Association and correlation of different chemotherapeutic regimens and doses with onset and severity of anemia among solid cancer patients

Hassan BA, Yusoff ZB, Hassali MA, Othman SB

Asian Pac J Cancer Prev, 2011;12(10):2753-8.
PMID: 22320987

INTRODUCTION: Anemia is considered as one of the most frequent hematological demonstration of malignant diseases, which lead to momentous impairment in every tissues and organs of cancer patients and put them under serious stress. This major problem may arise because of the underlining diseases (i.e., cancer diseases) or radiotherapy or chemotherapy treatment received. This present study tries to find the association between anemia onset and severity with different chemotherapeutics regimens used in the treatment of several solid cancers and to find the association of anemia onset and severity with different doses of these chemotherapeutics drugs.
METHODS: This retrospective observational study was conducted in Penang General Hospital on 534 anemic solid cancer patients who were admitted between 2003 and 2009. The main statistical tests used were Chi-square test and Logistic regression test for categorical data. While for continues data the main statistical tests were Linear regression and correlation test. The significance of the result will be when the P<0.05, while the confidence interval for this study was 95%.
RESULTS: FEC, 5-FU+5-FU, Docetaxel and Cisplatin+ 5-FU regimen has strong association and correlation with anemia onset and severity. However the associations and correlations with anemia severity were stronger than those with the onset. Different doses of 5-FU, cyclophosphamide, docetaxel and cisplatin play a critical role in anemia onset and severity.
CONCLUSION: Monitoring and determination of hemoglobin levels for cancer patients treated with FEC, 5-FU+5-FU, Docetaxel, Cisplatin+ 5-FU specifically with high doses must be emphasized and a focus of particular attention.

Matched MeSH terms: Piperidines/therapeutic use
Ifenprodil Reduced Expression of Activated Microglia, BDNF and DREAM Proteins in the Spinal Cord Following Formalin Injection During the Early Stage of Painful Diabetic Neuropathy in Rats

Ismail CAN, Suppian R, Ab Aziz CB, Long I

J Mol Neurosci, 2021 Feb;71(2):379-393.
PMID: 32671697 DOI: 10.1007/s12031-020-01661-1

The pharmacological inhibition of glial activation is one of the new approaches for combating neuropathic pain in which the role of glia in the modulation of neuropathic pain has attracted significant interest and attention. Neuron-glial crosstalk is achieved with N-methyl-D-aspartate-2B receptor (NMDAR-2B) activation. This study aims to determine the effect of ifenprodil, a potent noncompetitive NMDAR-2B antagonist, on activated microglia, brain-derived neurotrophic factors (BDNF) and downstream regulatory element antagonist modulator (DREAM) protein expression in the spinal cord of streptozotocin-induced painful diabetic neuropathy (PDN) rats following formalin injection. In this experimentation, 48 Sprague-Dawley male rats were randomly selected and divided into four groups: (n = 12): control, PDN, and ifenprodil-treated PDN rats at 0.5 μg or 1.0 μg for 7 days. Type I diabetes mellitus was then induced by injecting streptozotocin (60 mg/kg, i.p.) into the rats which were then over a 2-week period allowed to progress into the early phase of PDN. Ifenprodil was administered in PDN rats while saline was administered intrathecally in the control group. A formalin test was conducted during the fourth week to induce inflammatory nerve injury, in which the rats were sacrificed at 72 h post-formalin injection. The lumbar enlargement region (L4-L5) of the spinal cord was dissected for immunohistochemistry and western blot analyses. The results demonstrated a significant increase in formalin-induced flinching and licking behavior with an increased spinal expression of activated microglia, BDNF and DREAM proteins. It was also shown that the ifenprodil-treated rats following both doses reduced the extent of their flinching and duration of licking in PDN in a dose-dependent manner. As such, ifenprodil successfully demonstrated inhibition against microglia activation and suppressed the expression of BDNF and DREAM proteins in the spinal cord of PDN rats. In conclusion, ifenprodil may alleviate PDN by suppressing spinal microglia activation, BDNF and DREAM proteins.

Matched MeSH terms: Piperidines/therapeutic use*
Fulltext Efficacy and safety of fixed-dose combination therapy, alogliptin plus metformin, in Asian patients with type 2 diabetes: A phase 3 trial

Ji L, Li L, Kuang J, Yang T, Kim DJ, Kadir AA, et al.

Diabetes Obes Metab, 2017 05;19(5):754-758.
PMID: 28075066 DOI: 10.1111/dom.12875

This study evaluated the efficacy and safety of 26 weeks of twice-daily (BID) alogliptin + metformin fixed-dose combination (FDC) therapy in Asian patients with type 2 diabetes. Patients aged 18 to 75 years with hemoglobin A1c (HbA1c) of 7.5% to 10.0% after ≥2 months of diet and exercise and a 4-week placebo run-in were enrolled. Eligible patients were randomized (1:1:1:1) to placebo, alogliptin 12.5 mg BID, metformin 500 mg BID or alogliptin 12.5 mg plus metformin 500 mg FDC BID. The primary endpoint was change in HbA1c from baseline to end of treatment (Week 26). In total, 647 patients were randomized. The least-squares mean change in HbA1c from baseline to Week 26 was -0.19% with placebo, -0.86% with alogliptin, -1.04% with metformin and -1.53% with alogliptin + metformin FDC. Alogliptin + metformin FDC was significantly more effective ( P

Matched MeSH terms: Piperidines/therapeutic use*