Kl Bairy

Statin use and risk of diabetes mellitus

The 3-hydroxy-methylglutaryl coenzyme A reductase inhibitors, statins, are widely used in the primary and secondary prevention of cardiovascular diseases to lower serum cholesterol levels. As type 2 diabetes mellitus is accompanied by dyslipidemia, statins have a major role in preventing the long term complications in diabetes and are recommended for diabetics with normal low density lipoprotein levels as well. In 2012, United States Food and Drug Administration released changes to statin safety label to include that statins have been found to increase glycosylated haemoglobin and fasting serum glucose levels. Many studies done on patients with cardiovascular risk factors have shown that statins have diabetogenic potential and the effect varies as per the dosage and type used. The various mechanisms for this effect have been proposed and one of them is downregulation of glucose transporters by the statins. The recommendations by the investigators are that though statins can have diabetogenic risk, they have more long term benefits which can outweigh the risk. In elderly patients and those with metabolic syndrome, as the risk of diabetes increase, the statins should be used cautiously. Other than a subset of population with risk for diabetes; statins still have long term survival benefits in most of the patients.

Evaluation of antiinflammatory activity of Tephrosia purpurea in rats

Objective: To evaluate the antiinflammatory activity of orally administered ethanolic extract of Tephrosia purpurea in acute and subacute inflammation in rats. Methods: An ethanolic extract of Tephrosia purpurea was prepared. Carrageenan induced paw edema and cotton pellet granuloma were the models for acute and subacute inflammation respectively. Four groups of rats in each model were treated orally with 2% gum acacia, 100 mg /kg of aspirin, 500 mg/kg and 1 000 mg/kg of ethanolic extract of Tephrosia purpurea respectively. In carrageenan induced paw edema model, subplantar injection of 1% carrageenan was made into the hind paw of the rats sixty minutes after the administration of the respective drugs. The paw volume was measured immediately after injection of carrageenan, at 3 hours and at 6 hours. Then percentage inhibition of edema was calculated. In the cotton pellet granuloma model,animals were administered drugs for six days after placing cotton pellets in the axilla on each side. On the 7th day, dry weight of granuloma was calculated. Results: The rats treated with Tephrosia purpurea did not exhibit any significant decrease in paw volume and serum ceruloplasmin levels as compared to the control and aspirin treated groups in the acute inflammation model; while, there was a significant (P < 0.01) decrease in the weight of granuloma in Tephrosia purpurea and aspirin treated groups as compared to control in subacute inflammation. Conclusions: The ethanolic extract of orally administered Tephrosia purpurea shows significant antiinflammatory effect in subacute inflammation but not in acute inflammation in rats.

Evaluation of diuretic activity of Amaranthus spinosus Linn. aqueous extract in Wistar rats

ETHNOPHARMACOLOGICAL RELEVANCE Traditional Siddha medicine literature claims that the Amaranthus spinosus Linn. (family: Amaranthaceae) whole plant possesses diuretic property. AIM OF THE STUDY To evaluate the diuretic potential of Amaranthus spinosus aqueous extract (ASAE) in rats. MATERIAL AND METHODS Different concentrations of ASAE (200, 500, 1000, 1500mg/kg), thiazide (10mg/kg) and vehicle were orally administered to rats (n=6 animals per group) and their urine output was collected after 24h. Volume, pH, Na(+), K(+) and Cl(-) concentrations of urine were estimated. RESULTS ASAE produced increase in Na(+), K(+), Cl(-) excretion, caused alkalinization of urine, showed strong saluretic activity and carbonic anhydrase inhibition activity. These effects were observed predominantly at 500mg/kg dose and there was no dose-response relationship. CONCLUSION Our study strongly suggests that the Amaranthus spinosus is acting as a thiazide like diuretic with carbonic anhydrase inhibitory activity which restates the claim as diuretic herb in Siddha medicine.

Evaluation of the effect of Ferula asafoetida Linn. gum extract on learning and memory in Wistar rats

Objective: Memory loss is universal and is the first symptom to manifest in majority of the patients suffering from Alzheimers disease. This study is designed to investigate the effect of Ferula asafoetida linn. (F. foetida) extract on learning and memory in rats. Materials and Methods: Learning and memory were evaluated using elevated plus maze and passive avoidance paradigm after the oral administration of two doses (200 mg/kg and 400 mg/kg) of F. foetida aqueous extract with rivastigmine as positive control. Brain cholinesterase activity, serum thiols and cholesterol were also estimated. Results: Extract produced significant improvement in memory score i.e. step through latency at 400 mg/kg dose in passive avoidance model (P< 0.05) and dose-dependent improvement of transfer latency in elevated plus maze model (P< 0.001). Dose-dependent inhibition of brain cholinesterase (P< 0.001) and significant improvement in antioxidant levels (P< 0.05) were also noted. Conclusions: Memory enhancing potential of F. foetida can be attributed to acetylcholinesterase inhibiting and antioxidant properties. Hence, dietary usage of F. foetida is beneficial and can also be employed as an adjuvant to existing anti-dementia therapies.

Cortico-hippocampal salvage in chronic aluminium induced neurodegeneration by Celastrus paniculatus seed oil: Neurobehavioural, biochemical, histological study

OBJECTIVE To investigate the effects of Celastrus paniculatus seed oil in preventing the onset of chronic aluminum induced cortico-hippocampal neurodegeneration and oxidative stress. MATERIALS AND METHODS An animal model of senile dementia of Alzheimers type was produced by administering aluminum as aluminum chloride (4.2 mg/kg) intraperitoneally to male Wistar rats for 60 days and results compared to untreated control. Neurobehavioral investigations of Morris water maze tests, passive avoidance test, rotarod test and biochemical estimations of acetylcholineterase, malondialdehyde, glucose-6-phosphate dehydrogenase, superoxide dismutase, and hemoglobin in blood were performed fortnightly which gauged the extent of global oxidative stress and progressive neural damage. Findings were fortified by the above enzyme assays and histology of brain at necropsy. Prophylactic oral C. paniculatus in two doses 0.5 ml and 1 ml, were given to animals and the results were analyzed in comparison to a similar rodent model with standard drug donepezil (0.5 mg/kg) intraperitoneally. RESULTS C. paniculatus showed a significant prevention in onset of aluminum induced neural insult and overall systemic oxidative stress which was corroborated by the enlisted neurobehavioral, biochemical, and histological evidence. CONCLUSION C. paniculatus is a putative decelerator of Al-mediated Alzheimers like pathobiology.

Comparison of the efficacy of carbamazepine, gabapentin and lamotrigine for neuropathic pain in rats

Background: Neuropathic pain in cancer patients remain a treatment challenge. Many of the anticancer drugs have to be abandoned because patients develop neuropathic pain. Several antiepileptic drugs like carbamazepine, phenytoin, lamotrigine, felbamate are effective in neuropathic pain and trigeminal neuralgia. However, their efficacy varies. Aim: The aim of this study is to compare the efficacy of antiepileptic drugs in neuropathic pain induced by anticancer drugs. Materials and Methods: Neuropathic pain was induced in rats by injecting 4 doses of paclitaxel. The rats were divided into four groups of six animals each. Group I was treated with oral carbamazepine (cbz) 100 mg/kg, group II received oral gabapentin (gbp) 60 mg/kg, and group III was treated with oral lamotrigine (lam) 40 mg/kg and group IV was the control group. Behavioural testing for thermal hyperalgesia and mechanical hyperalgesia was assessed from 26th day of paclitaxel administration to next five days by hot plate method and Randall Siletto test, respectively, in all the four groups. One way analysis of variance followed by Scheffes post hoc test was used for statistical analysis. Results: In thermal hyperalgesia lam treated group was found to be significantly (P < 0.001) superior to cbz and gbp treated group. In mechanical hyperalgesia, lam group showed significant response (P < 0.05) as compared to gbp group. However, the gbp treated group showed a significant (P < 0.01) improvement after three days of treatment. Conclusions: In paclitaxel induced neuropathic pain, lamotrigine appears to be a promising drug. The difference in responses shown by different antiepileptics’ depends on the etiology of the underlying mechanisms in neuropathic pain.

DNA Methylation and Chromatin Remodeling: The Blueprint of Cancer Epigenetics

Epigenetics deals with the interactions between genes and the immediate cellular environment. These interactions go a long way in shaping up each and every persons individuality. Further, reversibility of epigenetic interactions may offer a dynamic control over the expression of various critical genes. Thus, tweaking the epigenetic machinery may help cause or cure diseases, especially cancer. Therefore, cancer epigenetics, especially at a molecular level, needs to be scrutinised closely, as it could potentially serve as the future pharmaceutical goldmine against neoplastic diseases. However, in view of its rapidly enlarging scope of application, it has become difficult to keep abreast of scientific information coming out of various epigenetic studies directed against cancer. Using this review, we have attempted to shed light on two of the most important mechanisms implicated in cancer, that is, DNA (deoxyribonucleic acid) methylation and histone modifications, and their place in cancer pathogenesis. Further, we have attempted to take stock of the new epigenetic drugs that have emerged onto the market as well as those in the pipeline that offer hope in mankinds fight against cancer.

Effect of imatinib on the biochemical parameters of the reproductive function in male swiss albino mice

Background: Treatment of cancers with cytotoxic agents such as tyrosine kinase inhibiting drugs often, but not always, result in transient to permanent testicular dysfunction. Germ cells are important targets of many chemicals. Most of the drugs are genotoxins and induce irreversible effect on genetic makeup. These mutagenic changes are proportionally related to carcinogenesis. This is alarmingly dangerous in youth and children, since these effects last longer, affecting fertility or forming basis for carcinogenesis. There is paucity of reports on planned studies of imatinib on the testicular function. Hence, the study was planned to assess the effects of imatinib on biochemical markers of testicular functions in male Swiss albino mice. Materials and Methods: Male Swiss albino mice were treated with imatinib and sacrificed at the end of first, second, fourth, fifth, seventh, and tenth week after the last exposure to imatinib. The testis were removed, weighed, and processed for biochemical analysis. Results: The intratesticular testosterone level was significantly (P<0.001) reduced in treated groups and severe effect was observed on week 4 and 5. The intratesticular lactate dehydrogenase (LDH) level was significantly increased by imatinib in all treated groups up to week 5. Conclusion: Imatinib does affect testosterone and LDH level significantly, but this effect is reversible once the drug is withdrawn. This finding may help the clinicians to plan and address the fertility-related issues in young patients of reproductive age who are being treated with imatinib for gastrointestinal tumors and chronic myeloid leukemia.

Pattern of adverse drug reactions due to cancer chemotherapy in a tertiary care hospital in South India.

Purpose: Studies regarding pattern of adverse drug reactions (ADRs) in cancer chemotherapy patients are scarce in India. This study was conducted to evaluate the pattern of occurrence of ADRs due to cancer chemotherapy in hospitalized patients and to assess the causality, severity, predictability, and preventability of these reactions. Materials and Methods: This was a retrospective, descriptive study and the occurrence and nature of ADR, suspected drug, duration of hospital stay and outcome were noted from case records. These ADRs were assessed for causality using both World Health Organization (WHO) causality assessment scale and Naranjos algorithm. The severity and preventability of the reported reactions were assessed using modified Hartwig and Siegel scale and modified Schumock and Thornton scale respectively. Results: Five hundred ADRs were recorded from 195 patients. Most common ADRs were infections (22.4%), nausea/vomiting (21.6%) and febrile neutropenia (13%). Platinum compounds, nitrogen mustards, taxanes, antibiotics and 5-fluorouracil were the most common drugs causing ADRs. WHO causality assessment scale showed 65% of the reactions to be “probable” and 35% to be “possible”, while Naranjos algorithm indicated that 65.6% of ADRs were “probable” and 34.4% were “possible”. Modified Hartwig and Siegel scale showed most reactions (41.4%) to be of “moderate level 4(a)” severity, while 30.6% of reactions were of “mild level 1” severity. About 30.8% of the ADRs were “definitely preventable” according to the modified Schumock and Thornton scale. Conclusion: ADRs are most important causes of morbidity and mortality and increase the economic burden on patient and society. By careful ADR monitoring, their incidence can be decreased.

Adverse Reactions of Ferric Carboxymaltose

The author reports a 55-year-old female diagnosed of chronic kidney disease grade-5 with associated co-morbidities like type 2 diabetes mellitus, diabetic retinopathy and hypothyroidism was admitted for arteriovenous fistula construction. She was started on ferric carboxymaltose for the treatment of anaemia. She was given a test dose before administering the drug intravenously and she did not develop any reaction. The drug ferric carboxymaltose was then administered over a period of one hour. About half an hour after drug administration, the patient developed breathlessness and myalgia. After half hour of the above episode of breathlessness and myalgia she also developed vomiting (one episode). Patient was managed with oxygen therapy, IV fluids and other drugs like corticosteroids, phenaramine maleate and nalbuphine which controlled the above symptoms.