Effectiveness of medicine Malaria Off 200 as mass prophylaxis against Malaria in the high-risk villages of Shahdol, Madhya Pradesh

Background: Learning from the past experiences, the district health authority Shahdol has planned a mass-prophylactic activity with the Homeopathy Medicine (Malaria Off 200) in the selected high-risk villages (above 5 API) in the year 2016 Objective: The present paper reports the effectiveness of Malaria off 200 as mass-prophylactic drug in addition to routine antimalarial activities under NVBDCP in district Shahdol, Madhya pradesh in year 2016. Methodology: A Homeopathic drug Malaria Off 200 was used for the mass-prophylaxis of  Malaria in high malaria transmission season in selected 28 villages of district Shahdol. The effectiveness of the drug was ascertained as “Reduction of ≥20% villages, having more than 2 malaria case in six-month period (July-December 2016)in comparison to the previous year”. Result: Of the 28 villages, seven (25%) reported Malaria case  incidence equal to or less than two in six-month period (July-December 2016). In the same time period in previous year 23 (82%) villages reported Malaria case  incidence more than two. So, reduction of number of villages with 'biannual Malaria case  incidence’ rate was 57%. Conclusion: The short term finding validate the campaign as effective, as per the operational definition of effectiveness coined for the campaign. However, further time series studies with Autoregressive Integrated Moving Average (ARIMA) is recommended for future.

Barriers of Treatment-Supporters for DOTS under RNTCP in District Shahdol, India: A Mix-Method Study

Background: One of the challenges of Revised National Tuberculosis Control Programme (RNTCP) has been that it has not been able to impart adequate knowledge, satisfactory attitude and desirable practices among treatment-supporters of rural and tribal communities. Present study was planned to explore the knowledge, attitude, practice and perceived barriers related to Directly Observed treatment (DOT) provision among the treatment-supporters of Shahdol district, Madhya Pradesh in 2018. Methods: Mixed–methods study design of triangulation type was used among 30 community- based treatment-supporters of DOT from Sohagpur tahsil of district Shahdol of Madhya Pradesh, India. The cross-sectional quantitative component assessed the knowledge, attitude and practices and three focus-group discussions were used to explore the perceived barriers related to DOT provision. Results: ‘Adequate knowledge’ related to DOT provision was found in 37% of treatment- supporters, while 40% had “satisfactory attitude” and 60 % had “satisfactory practice” related to DOT. The focus-group discussions revealed, ineffective training, lack of supportive supervision, insecure monetary incentive, distant Public Health Institution/Designated Microscopic Center, language barrier and patient related stigma to TB disease as main perceive challenges related to DOT. Conclusion: Study revealed inadequate knowledge and unsatisfactory attitude and practice related to DOT provision among treatment-supporters. Effective training, making services accessible to patient, making RNTCP form in Hindi language and strengthening of honorarium disbursement mechanism are urgently required.

To establish the reference range of glycated hemoglobin.

Background: Diabetes mellitus (DM) has emerged as a major healthcare problem in India. There were an estimated 40 million persons with DM in India in 2007 and this number is predicted to rise to almost 70 million by 2025. It is estimated that every fifth person with diabetes will be an Indian. The objective of the present investigation was to establish the reference range for glycated hemoglobin (HbA1C) in healthy non-diabetic subjects in our hospital laboratory and compare it with the values reported by standard laboratories. Methods: The study was conducted in the Department of Biochemistry, MMIMSR, Mullana (Ambala, Haryana). Total number of subjects was 50 (25 males, 25 females), aged 30 to 70 years. 2 ml of blood was collected from antecubital vein under aseptic conditions from each subject and put in EDTA vials. Hemolysed blood was estimated by semiautoanalyzer for HbA1C. Results: In females, the levels were 6.50 ± 0.74 % while in males the levels were 6.27 ± 0.94 %. The overall range in females was 4.8 - 7.56 % while in males it was 4.2 to 7.56 %. The values were comparable (p>0.05) with those reported by standard laboratories, e.g. Dr. Lal PathLabs (<6%), Charak diagnostic (4.5-6.3%) and Mayo Clinic (6.5-7%). Conclusion: Our laboratory levels of HbA1C are comparable with the reference range of different laboratories and hence suitable to be used as cut-offs while interpreting the results of patients with DM.

Molecular insights into diabetic cardiomyopathy.

Diabetes mellitus affects the heart in 3 ways: (1) coronary artery disease (CAD) due to accelerated atherosclerosis; (2) cardiac autonomic neuropathy (CAN); and (3) diabetic cardiomyopathy (DbCM). Although there is high awareness among clinicians about the first two entities, DbCM is poorly recognized by most physicians and diabetologists. DbCM, first described by Rubler et al. in 1972, is defined as myocardial dysfunction occurring in patients with diabetes in the absence of CAD, hypertension, or valvular heart disease. The development of DbCM is multi-factorial including autonomic dysfunction, metabolic derangements, abnormalities in ion homeostasis, alteration in structural proteins, and interstitial fibrosis. Chronic hyperglycemia is thought to play a central role in the development of DbCM. The main metabolic abnormalities in diabetes are hyperglycemia, hyperlipidemia and inflammation, all of which stimulate generation of reactive oxygen/nitrogen species which result in reduction of myocardial contractility and acceleration of fibrosis besides cellular DNA damage and cardiomyocyte apoptosis. In addition, advanced glycation end products (AGEs) indirectly exert their detrimental effect on the myocardium by interacting and up-regulating their receptors, including receptors of AGE and galectin-3. This results in activation of transcription factors, such as nuclear factor-kB (NF-kB). The NF-kB dependent genes, in turn, trigger several pathways that induce production of pro-inflammatory cytokines and cause myocardial damage. All these molecular events are potential therapeutic targets in DbCM.

Duxorubicin-induced cardiotoxicity.

The survival rate of cancer patients has greatly increased over the last 20 years. However, to achieve this result, a considerable price has been paid in terms of the side-effects associated with the intensive anticancer treatment. Cardiotoxicity of anticancer drugs is a serious problem. It is defined, by the National Cancer Institute, as the “toxicity that affects the heart.” This definition not only includes a direct effect of the drug on the heart, but also an indirect effect due to enhancement of hemodynamic flow alterations or due to thrombotic events. Cardiotoxicity can develop in a subacute, acute, or chronic manner. The risk for such effects depends upon: cumulative dose, rate of drug administration, mediastinal radiation, advanced age, younger age, female gender, pre-existing heart disease and hypertension. Anthracyclines, such as doxorubicin (DOX), cause serious cardiac side-effects. Acute tachyarrhythmias and acute heart failure (HF) may occur after high doses, but these reactions are now rare due to changed dosage schemes (e.g. slower infusion) with the aim to prevent this. However, the sub-acute or chronic cardiac effects of anthracyclines remain a clinical problem. Clinically, anthracycline induced cardiotoxicity manifests itself as left ventricular failure, which develops insidiously over months to years after completion of the anthracycline based chemotherapy and may result in congestive HF. The mechanism of anthracyclin induced cardiotoxicity is not totally unraveled. It is likely that the decline in myocardial function is related to apoptosis of cardiac myocytes that occurs apparently at random in the myocardium. Anthracyclin induced formation of reactive oxygen species (ROS) in the presence of intracellular iron, impaired homeostasis of intracellular iron and calcium (that may facilitate the apoptosis induced by the ROS) have been put forward as mechanisms. Cardiac protection can be achieved by limitation of the cumulative dose. Further, addition of the antioxidant and iron chelator dexrazoxane to anthracycline therapy has shown to be effective in lowering the incidence of anthracycline induced cardiotoxicity.

Serum Magnesium Levels: A Key Issue For Diabetes Mellitus.

The global burden of diabetes mellitus is expected to increase by 42% (from 51 million in year 1995 to 72 million by 2025) and by 172% (from 84 to 288 million) in the developed countries. The disease leads to many complications and one of them is electrolyte imbalance which has been an ignored subject. Amongst the electrolytes, magnesium merits special attention. The aim of the present study was to assess serum magnesium levels in Type 2 diabetics. A hospital based cross- sectional study was performed on 50 diabetic patients attending the OPD of medicine department from January 2011 to July 2011, M.M. Institute of Medical Sciences and Research, Mullana (Ambala). Thirty age-matched healthy controls were also selected for the sake of comparison. Blood was withdrawn and serum magnesium levels were estimated by colorimetric method using Xylidyl blue dye. The results were analyzed using Student's unpaired 't'test. Serum magnesium levels among normal healthy controls (n=30) ranged between 1.8-3.0 mg /dl (mean ±SD = 2.33±0.37 mg/dl), while the levels of serum magnesium in diabetic patients (n=50) ranged between 0.2-2.25 mg/dl (mean ±SD = 1.62±0.47). The difference was statistically significant (p<0.001). Levels of serum magnesium were significantly lower in diabetic patients as compared to normal healthy controls. Therefore, hypomagnesaemia is a key issue in diabetes which, if corrected, is expected to result in a better management of the disease.

Continuous arteriovenous haemofiltration to regulate hyperkalaemia during renal transplantation: a case report.

Progressive hyperkalaemia is common in end stage renal disease patients waiting for renal transplantation. Ventricular tachycardia and ventricular fibrillation due to hyperkalaemia are life-threatening complications in these patients. In live and related renal transplant, after induction and anaesthesia, ventricular fibrillation and pulmonary oedema occurred. After immediate resuscitation by defibrillation and intravenous injection of adrenaline, the patient was put on continuous femoral arteriovenous haemofiltration (CAVH). This improved his pulmonary oedema, controlled hyperkalaemia and surgery could be completed uninterruptedly. After anaesthetising live and related kidney donor for nephrectomy, since it is not prudent to stop recipient surgery because of unforeseen complication, the authors wish to recommend CAVH as an alternative method to prevent life threatening cardiac complication of hyperkalaemia.

Alginate nanoparticles as antituberculosis drug carriers: formulation development, pharmacokinetics and therapeutic potential.

BACKGROUND: Reduction in the dosing frequency of antituberculosis drugs (ATDs) by applying drug delivery technology has the potential to improve the patient compliance in tuberculosis (TB). Alginate (a natural polymer) based nanoparticulate delivery system was developed for frontline ATDs (rifampicin, isoniazid, pyrazinamide and ethambutol). METHODS: Alginate nanoparticles were prepared by the controlled cation induced gelification method and administered orally to mice. The drug levels were analysed by high performance liquid chromatography (HPLC) in plasma/tissues. The therapeutic efficacy was evaluated in M. tuberculosis H37Rv infected mice. RESULTS: High drug encapsulation efficiency was achieved in alginate nanoparticles, ranging from 70%-90%. A single oral dose resulted in therapeutic drug concentrations in the plasma for 7-11 days and in the organs (lungs, liver and spleen) for 15 days. In comparison to free drugs (which were cleared from plasma/organs within 12-24 h), there was a significant enhancement in the relative bioavailability of encapsulated drugs. In TB-infected mice three oral doses of the formulation spaced 15 days apart resulted in complete bacterial clearance from the organs, compared to 45 conventional doses of orally administered free drugs. CONCLUSIONS: Alginate nanoparticles appear to have the potential for intermittent therapy of TB.

Oral poly(lactide-co-glycolide) nanoparticle based antituberculosis drug delivery: toxicological and chemotherapeutic implications.

The present study reports on the detailed toxicological and chemotherapeutic evaluation of antituberculosis drug loaded nanoparticles in mice. A single oral dose administration of poly(lactide-co-glycolide) (PLG, a synthetic polymer) nanoparticles containing rifampicin+isoniazid+pyrazinamide+ethambutol could maintain drug levels in various tissues for 9-10 days and did not elicit any adverse response even when administered at several fold higher than the recommended therapeutic dose. However, dosing with conventional free drugs at the equivalent higher doses was lethal. Despite multiple oral dosing with the formulation at every 10th day, no toxicity was observed on the completion of subacute (28 days) or chronic (90 days) toxicity studies based on survival, gross pathology, histopathology, blood biochemistry and hematology. In mice harboring a high mycobacterial load (mimicking human tuberculosis), two independent chemotherapeutic regimens, i.e. 5 doses of PLG nanoparticles encapsulating (rifampicin+isoniazid+pyrazinamide+ethambutol) administered 10 days apart, or 2 doses of the 4-drug formulation followed by 3 doses of 2-drug formulation (rifampicin+isoniazid) resulted in undetectable bacilli. Further, the efficacy was comparable to 46 daily doses of oral free drugs. Therefore, the experimental evidence suggests that PLG nanoparticle-based antituberculosis drug delivery system is safe and well suited for prolonged and intermittent oral chemotherapy.

Nanotechnology based drug delivery system(s) for the management of tuberculosis.

The era of nanotechnology has allowed new research strategies to flourish in the field of drug delivery. Nanoparticle-based drug delivery systems are suitable for targeting chronic intracellular infections such as tuberculosis. Polymeric nanoparticles employing poly lactide-co-glycolide have shown promise as far as intermittent chemotherapy in experimental tuberculosis is concerned. It has distinct advantages over the more traditional drug carriers, i.e. liposomes and microparticles. Although the experience with natural carriers, e.g. solid lipid nanoparticles and alginate nanoparticles is in its infancy, future research may rely heavily on these carrier systems. Given the options for oral as well as parenteral therapy, the very nature of the disease and its complex treatment urges one to emphasize on the oral route for controlled drug delivery. Pending the discovery of more potent antitubercular drugs, nanotechnology-based intermittent chemotherapy provides a novel and sound platform for an onslaught against tuberculosis.

Scorpion sting envenomation presenting with pulmonary edema in adults: a report of seven cases from Nepal.

Scorpion sting is a common problem in villages of Eastern Nepal. The life-threatening complications of myocarditis and pulmonary edema is known in red scorpion in India but not reported in Nepal. This condition requires urgent attention and ICU care from few hours to days. Delay in recognition and the hypoxemia increase the morbidity and mortality. Illiteracy, ignorance, poverty, traditional faith healers trying treatment in remote areas, lack of transport in difficult terrains and the non availability of ventilation facility in nearby hospital, add to delay in appropriate treatment. Seven young adult patients admitted in a span of two years with history of scorpion sting presenting with pulmonary edema required ICU care. They were successfully managed with the positive pressure ventilation with PEEP, cardiac support with inotropes and fluid balance. Magnitude of problem, clinical presentation and management done is emphasized.

Liposomes as adjuvant for anti-mycobacterial vaccine development.

Mycobacteria are intracellular pathogens that invade and reside inside the macrophages. Recent advances in controlled delivery systems for vaccines such as liposomes have sparked a renewed interest in their potential application for the prevention of mycobacterial infections. The versatility of liposomes in the incorporation of hydrophilic/hydrophobic components, their non-toxic nature, biodegradability, biocompatibility, adjuvanticity, induction of cellular immunity, property of sustained release and prompt uptake by macrophages, makes them attractive candidates for the delivery of antigens. This review focuses on liposome research in the area of mycobacterial diseases and highlights how the various mycobacterial components may be exploited as powerful antigens with liposomes as adjuvants.

Lung specific stealth liposomes as antitubercular drug carriers in guinea pigs.

The problem of patient non-compliance in the management of tuberculosis (TB) can be overcome by reducing the dosing frequency of antitubercular drugs (ATD) employing drug carriers. This study reports on the intravenous (iv) administration of lung specific stealth liposomes encapsulating ATD (rifampicin and isoniazid in combination) to guinea pigs and the detailed pharmacokinetic/chemotherapeutic studies. Following a single iv administration of liposomal drugs, the latter were found to exhibit sustained therapeutic levels in plasma for 96-168 hr with half-lives of 24-70 hr, mean residence time (MRT) of 35-81 hr and organ drug levels up to day 7. The relative bioavailability (as compared to oral free drugs) was increased by 5.4-8.9 folds, whereas the absolute bioavailability (as compared to iv free drugs) was increased by 2.9-4.2 folds. Weekly therapy with liposomal ATD for 6 weeks produced equivalent clearance of Mycobacterium tuberculosis from organs as did daily therapy with oral free drugs. Hence, intravenous liposomal ATD offer the therapeutic advantage of reducing the dosing frequency and improving the patient compliance in the management of TB.