Impact of empagliflozin add-on therapy on quality of life in patients of type 2 diabetes mellitus with hypertension: A prospective study.

Background: Diabetes has a negative impact on patient's quality of life (QoL). Comorbidities and polypharmacy further worsen their QoL. Thus, in addition to glycemic control, assessment of QoL is also gaining importance. Objective: The objective of this study was to evaluate QoL in patients of type 2 diabetes mellitus (T2DM) with hypertension after add-on empagliflozin to triple drug therapy (metformin, teneligliptin, and glimepiride). Materials and Methods: A prospective research was done on T2DM patients with hypertension, who visited a tertiary care referral institute's endocrine outpatient clinic. For 3 months, empagliflozin, 25 mg once daily, was administered as an add-on treatment with metformin, teneligliptin, and glimepiride. In addition to clinical assessment, an Urdu-translated QoL instrument for Indian diabetes patients was used to conduct QoL study. The QoL outcomes prior to empagliflozin add-on were compared with those obtained at the conclusion of the 3 months of treatment. Results: Empagliflozin as an add-on therapy significantly improved various aspects of QoL like role limitation due to physical health, physical endurance, general health, symptom botherness, financial worries, emotional/mental health, and diet satisfaction (P < 0.001). It also improved glycemic and blood pressure parameters significantly. Conclusion: QoL is an essential measure with respect to patient-centered treatment approach. Empagliflozin, as an add-on medication, improved QoL, glycemic parameters and blood pressure in T2DM patients with hypertension. It can be recommended as an add-on, but more research with a larger sample size is required.

Role of drugs in the prevention and amelioration of radiation induced toxic effects.

As the use of radiation technology for nuclear warfare or for the benefits of mankind (e.g. in radiotherapy or radio-diagnosis) is increasing tremendously, the risk of associated side effects is becoming a cause of concern. These effects, ranging from nausea/vomiting to death, may result from accidental or deliberate exposure and begin in seconds. Through this review paper, efforts have been done to critically review different compounds which have been investigated as radioprotectors and radiation mitigators. Radioprotectors are compounds which are administered just before or at the time of irradiation so as to minimize the radiation induced damage to normal tissues. And radiation mitigators are the compounds which can even minimize or ameliorate post irradiaion-toxicity provided they are administered before the onset of toxic symptoms. A variety of agents have been investigated for their preventive and ameliorative potential against radiation induced toxic effects. This review article has focused on various aspects of the promising representative agents belonging to different classes of radioprotectors and mitigators. Many compounds have shown promising results, but till date only amifostine and palifermin are clinically approved by FDA. To fill this void in pharmacological armamentarium, focus should be shifted towards novel approaches.

Chemopreventive effect of artesunate in 1,2-dimethylhydrazine-induced rat colon carcinogenesis.

Artesunate (ART) is a semisynthetic derivative of artemisinin. Artemisinin and its derivatives have shown profound cytotoxicity and antitumor activity in addition to antimalarial activity in various studies. As the in vivo chemopreventive efficacy of ART in colon carcinogenesis has not been investigated so far, the aim of the current study was to study the chemopreventive effect of ART in 1,2-dimethylhydrazine (DMH)-induced rat colon carcinogenesis. Animals were divided into four groups (n = 6): Group I - vehicle (1 mM ethylenediaminetetraacetic acid), Group II - DMH (20 mg/kg), Group III - DMH + 5-fluorouracil (81 mg/kg), Group IV - DMH + ART (6.7 mg/kg). After completion of 15 weeks of treatment, rats were sacrificed under ether anesthesia by cervical dislocation for assessment of lipid peroxidation (LPO), antioxidant status, average number of aberrant crypt foci (ACF), and cytokine levels. ART administration significantly decreased the average number of ACF/microscopic field. Similarly, LPO level was decreased and antioxidant activities were enhanced after ART treatment. ART decreased the levels of proinflammatory cytokines and induced apoptosis in the colons of DMH-treated rats. The results of this study suggest that ART has a beneficial effect against chemically induced colonic preneoplastic progression in rats.

Effect of goat milk on hepatotoxicity induced by antitubercular drugs in rats.

Aim of the present study was to assess the hepatoprotective activity of goat milk on antitubercular drug-induced hepatotoxicity in rats. Hepatotoxicity was induced in rats using a combination of isoniazid, rifampicin, and pyrazinamide given orally as a suspension for 30 days. Treatment groups received goat milk along with antitubercular drugs. Liver damage was assessed using biochemical and histological parameters. Administration of goat milk (20 mL/kg) along with antitubercular drugs (Group III) reversed the levels of serum alanine aminotransferase (82 ± 25.1 vs. 128.8 ± 8.9 units/L) and aspartate aminotransferase (174.7 ± 31.5 vs. 296.4 ± 56.4 units/L, p<0.01) compared with antitubercular drug treatment Group II. There was a significant decrease in serum alanine aminotransferase (41.8 ± 4.1 vs. 128.8 ± 8.9 ​ units/L, p<0.01) and aspartate aminotransferase (128.8 ± 8.54 vs. 296.4 ± 56.4 units/L, p<0.001) levels in Group IV (goat milk 40 mL/kg) compared with antitubercular drug treatment Group II. Goat milk (20 mL/kg and 40 mL/kg) was effective in reversing the rise in malondialdehyde level compared with the antitubercular drug suspension groups (58.5 ± 2 vs. 89.88 ± 2.42 µmol/mL of tissue homogenate, p<0.001 and 69.7 ± 0.78 vs. 89.88 ± 2.42 µmol/mL of tissue homogenate, p<0.001, respectively). Similarly, both doses of milk significantly prevented a fall in superoxide dismutase level (6.23 ± 0.29 vs. 3.1 ± 0.288 units/mL, p<0.001 and 7.8 ± 0.392 vs. 3.1 ± 0.288 units/mL, p<0.001) compared with the group receiving antitubercular drugs alone. Histological examination indicated that goat milk reduced inflammation and necrotic changes in hepatocytes in the treatment groups. The results indicated that goat milk prevented the antitubercular drug-induced hepatotoxicity and is an effective hepatoprotective agent.

Correlation between Sleep Duration and Risk of Stroke.

Modern lifestyle and job requirements have changed the sleep habits of most of the adult population. Various population-based studies have associated an increase in mortality with either shortened sleep or long sleep duration. Thus a U-shaped relationship between sleep duration and all-cause mortality in both men and women has been suggested. Several studies have found an association between sleep duration and risk of cardiovascular diseases also. Efforts to understand the etiology of stroke have indicated an association between sleep and stroke too. Obstructive sleep apnea, a sleep-related disorder, has been reported to significantly increase the risk of stroke. Moreover, many studies have shown that both short and long sleep durations are related to increased likelihood of diabetes and hypertension, which themselves are risk factors for stroke. Therefore, this review focuses on the correlation between sleep duration and risk of stroke based on the experimental and epidemiologic studies. Although a few experimental studies have reported that partial sleep deprivation may reduce stroke incidence and severity, yet, most experimental and observational studies have indicated a strong association between short/long sleep durations and higher risk of stroke.

Role of vinpocetine in cerebrovascular diseases.

A cerebrovascular accident, or stroke, is defined as the abrupt onset of a neurological deficit, which can be due to ischemia. Cerebral ischemia is caused by a reduction in blood flow that thereby decreases cerebral metabolism. Chronic cerebral hypoperfusion leads to irreversible brain damage and plays an important role in the development of certain types of dementia. Vinpocetine, chemically known as ethyl apovincaminate, is a vinca alkaloid that exhibits cerebral blood-flow enhancing and neuroprotective effects. Non-clinical and clinical studies have suggested multiple mechanisms responsible for the beneficial neuroprotective effects of vinpocetine. As no significant side effects related to vinpocetine treatment have been reported, it is considered to be safe for long-term use. This vasoactive alkaloid is widely marketed as a supplement for vasodilation and as a nootropic for the improvement of memory. The present review focuses on studies investigating the role of vinpocetine in cerebrovascular diseases.

Dual inhibition: a novel promising pharmacological approach for different disease conditions.

To overcome the problems associated with polypharmacy, which include medication non compliance, adverse drug reactions, drug-drug interactions and increased pill-burden, various strategies, such as sustained-release drugs and fixed-dose combination regimens (polypills), have been developed. Out of these, a novel and very much promising approach is the use of dual-action drugs. Amongst the dual-action drugs, there is a class of compounds known as dual inhibitors, which possess the dual inhibitory activity. The most common examples of dual inhibitors are rivastigmine, ladostigil, asenapine, phenserine, amitriptyline, clomipramine, doxepin and desipramine. This review article focuses on the conventional drugs used in different diseases which possess dual inhibition activity as well as those which are still in the preclinical/clinical phase.

Lacosamide, a newer antiepileptic.

Lacosamide (LCM) is a newer antiepileptic drug with a dual mode of action. It selectively enhances slow inactivation of voltage-gated sodium channels without affecting fast inactivation, and modulates collapsing response mediator protein 2 (CRMP-2). It has a high oral bioavailability of approximately 100%. It has shown potent and broad neuroprotective effects in vitro and in vivo animal models making it a potential candidate for long term treatment of epilepsy. In addition to this, it has demonstrated analgesic activity in various animal models. Apart from this, LCM has demonstrated potent effects in animal models for a variety of CNS disorders like schizophrenia and stress induced anxiety. Various safety pharmacology and toxicology studies have shown that LCM is well tolerated. Clinical trials have also suggested that LCM is a safe, effective, and well tolerated adjunctive treatment for reduction of seizure frequency in patients with highly refractory, partial seizures. Other potential indications of LCM are being investigated.

Pharmacokinetic and toxicological profile of artemisinin compounds: an update.

Artemisinin has been used effectively in malaria treatment. With the emerging resistance to malaria, the optimum and judicial use of the drug has become important. The drug metabolism and toxicology can have an impact on the therapeutic profile and clinical use of this antimalarial agent. In this review, we discuss the pharmacokinetics and toxicological aspects of artemisinin and its therapeutic implications. Artemisinins have several dosing routes including oral, intramuscular, intravenous and rectal. With repeated dosing, artemisinin has propensity for autoinduction, leading to decreased plasma levels on repeated dosing. Combination with other antimalarials in most cases did not influence the pharmacokinetics of artemisinins. Interactions with cytochrome P(450) inhibitors are known but these neither affect the efficacy nor the toxicity of the respective derivative. Artemisinins are generally regarded to be of low toxicity. Two major problems associated with them are neurotoxicity and reproductive toxicity. But the extent of this neurotoxicity is dependent on the nature of the compound, on the route of administration, and on the nature of the formulation. Moreover, it occurs in humans at very high doses. However, as a matter of precaution, the use of artemisinins in the first trimester of pregnancy has been contraindicated.