Chlorogenic acid stabilized nanostructured lipid carriers (NLC) of atorvastatin: formulation, design and in vivo evaluation.

The present work was aimed at developing an optimized oral nanostructured lipid carrier (NLC) formulation of poorly soluble atorvastatin Ca (AT Ca) and assessing its in vitro release, oral bioavailability and pharmacodynamic activity. In this study, chlorogenic acid, a novel excipient having synergistic cholesterol lowering activity was utilized and explored in NLC formulation development. The drug-loaded NLC formulations were prepared using a high pressure homogenization technique and optimized by the Box-Behnken statistical design using the Design-Expert software. The optimized NLC formulation was composed of oleic acid and stearic acid as lipid phase (0.9% w/v), poloxamer 188 as surfactant (1% w/v) and chlorogenic acid (0.05% w/v). The mean particle size, polydispersity index (PDI) and % drug entrapment efficiency of optimized NLC were 203.56 ± 8.57 nm, 0.27 ± 0.028 and 83.66 ± 5.69, respectively. In vitro release studies showed that the release of drug from optimized NLC formulations were markedly enhanced as compared to solid lipid nanoparticles (SLN) and drug suspension. The plasma concentration time profile of AT Ca in rats showed 3.08- and 4.89-fold increase in relative bioavailability of developed NLC with respect to marketed preparation (ATORVA® tablet) and drug suspension, respectively. Pharmacodynamic study suggested highly significant (**p < 0.01) reduction in the cholesterol and triglyceride values by NLC in comparison with ATORVA® tablet. Therefore, the results of in vivo studies demonstrated promising prospects for successful oral delivery of AT Ca by means of its chlorogenic acid integrated NLC.

Neuroprotective potential of Betulinic acid against TIO2NP induced neurotoxicity in zebrafish.

Betulinic acid (BA) is a natural triterpenoid extracted from Bacopa monnieri. BA has been reported to be used as a neuroprotective agent, but their molecular mechanisms are still unknown. Therefore, in this study, we attempted to investigate the precise mechanism of BA for its protective effect against Titanium dioxide nanoparticles (TiO2NP) induced neurotoxicity in zebrafish. Hence, our study observation showed that 10 µg/ml dose of TiO2NP caused a rigorous behavioral deficit in zebrafish. Further, biochemical analysis revealed TiO2NP significantly decreased GSH, and SOD, and increased MDA, AChE, TNF-α, IL-1ß, and IL-6 levels, suggesting it triggers oxidative stress and neuroinflammation. However, BA at doses of 2.5,5,10 mg/kg improved behavioral as well as biochemical changes in zebrafish brain. Moreover, BA also significantly raised the levels of DA, NE, 5-HT, and GABA and decreased glutamate levels in TiO2NP-treated zebrafish brain. Our histopathological analysis proved that TiO2NP causes morphological changes in the brain. These changes were expressed by increasing pyknotic neurons, which were dose-dependently reduced by Betulinic acid. Likewise, BA upregulated the levels of NRF-2 and HO-1, which can reduce oxidative stress and neuroinflammation. Thus, our study provides evidence for the molecular mechanism behind the neuroprotective effect of Betulinic acid. Rendering to the findings, we can consider BA as a suitable applicant for the treatment of AD-like symptoms.

Glabridin mitigates TiO2NP induced cognitive deficit in adult zebrafish.

Glabridin is extracted from the roots of Glycyrrhiza glabra, which has anti-oxidative and anti-inflammatory properties. We investigated the neuroprotective potential of Glabridin against the learning and memory deficit by triggering NRF2/HO-1 signaling in Titanium dioxide nanoparticles (TiO2NP) treated zebrafish. Our study suggests that Glabridin at doses of 12.5, 25, and 50 mg/kg/day for 7 days improved memory and lowered anxiety in the novel object recognition test, T-maze, and novel diving tank respectively. Biochemical analysis showed that Glabridin treatment in TiO2NP-exposed zebrafish enhanced GSH, CAT, SOD, and GPx activity and reduced MDA levels; inhibited proinflammatory mediators, namely, TNF-α, IL-1ß, and IL-6. In histopathological evaluation, Glabridin significantly reduced pycnotic neurons in TiO2NP-treated zebrafish brains. Furthermore, Glabridin upregulated NRF2 and HO-1 levels, which leads to a decline in oxidative stress and neuroinflammation and were reversed by ML385 treatment. ML385 as a probe molecule that specifically inhibit NRF2 and prevents its downstream gene expression. Thus, these considerable outcomes provide new insights into the neuroprotective effect of glabridin.

Role of Nrf2 in Oxidative Stress, Neuroinflammation and Autophagy in Alzheimer's Disease: Regulation of Nrf2 by Different Signaling Pathways.

Alzheimer's disease (AD) is an age-dependent neurodegenerative disorder and the leading cause of dementia. AD is characterized by the aggregation of amyloid-ß (Aß) peptide, increased levels of tau protein, and loss of redox homeostasis responsible for mitochondrial dysfunction, oxidative stress, and neuroinflammation. Excessive accumulation of toxic Aß plaques activates microglia, which initiates neuroinflammation and consequently accelerates synaptic damage and neuronal loss. Various proinflammatory cytokines release, microglia proliferation, reactive astrocyte, and oxidative (reactive oxygen species (ROS) production, level of antioxidant enzymes, redox homeostasis, and lipid peroxidation) stress play a major role in AD. Several studies revealed that nuclear factor erythroid 2-related factor 2 (Nrf2) regulates redox homeostasis and works as an anti-inflammatory in various neurodegenerative disorders. D-Glutamate expression of transcription factor Nrf2 and its genes (glutamate-cysteine ligase catalytic subunit (GCLC), Heme oxygenase-1 (HO-1), and NADPH quinone oxidoreductase I (NQO1)) has been found in AD. Nrf2-HO-1 enhances the expression of antioxidant genes, inhibits microglia-mediated inflammation, and boosts mitochondrial function, suggesting that modulators of this protein may be useful to manage AD. This review focuses on the role of Nrf2 in AD, with a particular emphasis on the various pathways involved in the positive and negative modulation of Nrf2, namely Phosphoinositide 3-kinase (PI3K), Glycogen synthase kinase-3 (GSK-3), Nuclear factor kappa-B (NF-κB), and p38Mitogen-activated protein kinases (p38MAPK). Also, we have discussed the progress and challenges regarding the Nrf2 activators for AD treatment.

Phenotypic & molecular characterization of AmpC ß-lactamases among Escherichia coli, Klebsiella spp. & Enterobacter spp. from five Indian Medical Centers.

BACKGROUND & OBJECTIVES: AmpC ß-lactamases which are often plasmid mediated hydrolyze all ß-lactam antibiotics except cefepime and carbapenems. We evaluated the presence of AmpC ß-lactamases among Enterobacteriaceae strains recovered prospectively from patients at five Indian tertiary care centres. METHODS: The study included 909 consecutive Gram-negative isolates recovered from clinically significant specimens during June 2007 - May 2008 as part of an ICMR-ESBL study. Among the study isolates, 312 were found to be cefoxitin resistant by disc diffusion test (DDT). Minimum inhibitory concentration (MIC) determination by E test was done against amikacin, levofloxacin, impinem, meropenem, ertapenem, tigecycline and piperacillin-tazobactam. Combined DDT using phenyl boronic acid as inhibitor with cefoxitin was used for phenotypic confirmation of AmpC phenotype. The common Amp C genotypes ACC, FOX, MOX, DHA, CIT and EBC were detected by multiplex PCR. RESULTS: Plasmid mediated Amp C phenotype was confirmed in 114 of the 312 (36.5%) cefoxitin resistant isolates with 255 (81.7%) showing multidrug resistance. Susceptibility to tigecycline was highest (99%) followed by imipenem, meropenem (97%), ertapenem (89%), amikacin (85%), and piperacillin-tazobactam (74.6%). Levofloxacin resistance was 82 per cent. ESBL co carriage was observed among 92 per cent of Amp C producers. Among 114 Amp C producers, 48 could be assigned a genotype, this included CIT- FOX (n = 25), EBC (n = 10), FOX (n = 4), CIT (n = 3), EBC-ACC (n = 2) and one each of DHA, EBC-DHA, FOX -DHA and FOX-EBC-DHA. INTERPRETATION & CONCLUSIONS: Overall, AmpC phenotypes were found in 12.5 per cent isolates, multidrug resistance and ESBL co-carriage among them was high suggesting plasmid mediated spread. The study results have implications in rational antimicrobial therapy and continued surveillance of mechanisms of resistance among nosocomial pathogens.

Advances in pulmonary delivery of nanoparticles.

Nanotechnology has potential in the development of novel and effective delivery of drugs within lungs. Different strategies have been utilized for pulmonary delivery of drugs, including the use of lipid-based delivery systems (liposomes, ISCOMs, SLNs), use of polymeric matrix (PLGA, poly caprolactone, cynoacrylates, gelatin), development of polysaccharide particulates (chitosan, alginates, Carbopol, etc.), biocompatible metallic inorganic particles (iron, gold, zinc), etc. This paper reviews various nanopaticulate approaches in the form of lipids, polymers, metals, polysaccharides, or emulsions based for pulmonary drug delivery that could provide an increased biological efficacy and better local and systemic action.

AlCl3 induced learning and memory deficit in zebrafish.

Aluminium is a metal known to cause neurotoxicity in the brain, by promoting neurodegeneration and affecting memory and cognitive ability. AlCl3 has been reported to enhance reactive oxygen species (ROS) and inflammatory markers which are further responsible for the degeneration of neurons. AlCl3 exposure to zebrafish causes behavioral, biochemical, and neurochemical changes in the brain. In our study, Zebrafish were exposed to AlCl3 at three different doses (50 µg/L, 100 µg/L, and 200 µg/L) for four consecutive days. On days 1st and 4th, a novel diving test was performed to check anxiety in zebrafish. T - maze and novel object recognition test were used to check the memory on days 3rd and 4th with the help of ANY-maze software. On the last day (4th day), zebrafishes were sacrificed and whole brains were used to perform the biochemical, neurotransmitters, histopathological, and immunohistochemistry analysis. Our study revealed that AlCl3 exposure significantly decreased the total distance traveled, and the number of entries in the top zone and increased the time spent in the bottom zone, checked through the novel diving test. In the T maze test, AlCl3 treated zebrafish showed significantly increased transfer latency to the favorable zone and time spent, and the number of entries to the unfavorable zone. The exploration time with the novel object was reduced significantly after AlCl3 treatment. Moreover, reduced glutathione (GSH) and superoxide dismutase (SOD) levels were significantly reduced in AlCl3 treated zebrafish whereas malondialdehyde (MDA) level was found to be increased, indicating high oxidative stress. The neurotransmitters level was also disturbed indicated by the significantly decreased GABA, dopamine, noradrenaline, and Serotonin levels and increased glutamate level in the brain of zebrafish treated with AlCl3. Moreover, histopathological and immunohistochemistry study shows a markedly increased number of pyknotic neurons and reduced the expression of Nrf2 in the zebrafish brain after AlCl3 exposure. These findings suggest that AlCl3 significantly causes behavioral, biochemical, neurotransmitters, morphological, and molecular changes in zebrafish, ultimately causing AD.

MitoQ supplementation augments acute exercise-induced increases in muscle PGC1α mRNA and improves training-induced increases in peak power independent of mitochondrial content and function in untrained middle-aged men.

The role of mitochondrial ROS in signalling muscle adaptations to exercise training has not been explored in detail. We investigated the effect of supplementation with the mitochondria-targeted antioxidant MitoQ on a) the skeletal muscle mitochondrial and antioxidant gene transcriptional response to acute high-intensity exercise and b) skeletal muscle mitochondrial content and function following exercise training. In a randomised, double-blind, placebo-controlled, parallel design study, 23 untrained men (age: 44 ± 7 years, VO2peak: 39.6 ± 7.9 ml/kg/min) were randomised to receive either MitoQ (20 mg/d) or a placebo for 10 days before completing a bout of high-intensity interval exercise (cycle ergometer, 10 × 60 s at VO2peak workload with 75 s rest). Blood samples and vastus lateralis muscle biopsies were collected before exercise and immediately and 3 h after exercise. Participants then completed high-intensity interval training (HIIT; 3 sessions per week for 3 weeks) and another blood sample and muscle biopsy were collected. There was no effect of acute exercise or MitoQ on systemic (plasma protein carbonyls and reduced glutathione) or skeletal muscle (mtDNA damage and 4-HNE) oxidative stress biomarkers. Acute exercise-induced increases in skeletal muscle peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α) mRNA expression were augmented in the MitoQ group. Despite this, training-induced increases in skeletal muscle mitochondrial content were similar between groups. HIIT-induced increases in VO2peak and 20 km time trial performance were also similar between groups while training-induced increases in peak power achieved during the VO2peak test were augmented in the MitoQ group. These data suggest that training-induced increases in peak power are enhanced following MitoQ supplementation, which may be related to the augmentation of skeletal muscle PGC1α expression following acute exercise. However, these effects do not appear to be related to an effect of MitoQ supplementation on exercise-induced oxidative stress or training-induced mitochondrial biogenesis in skeletal muscle.

Structure based designing of thiazolidinone-pyrimidine derivatives as ERK2 inhibitors: Synthesis and in vitro evaluation.

Breast cancer has been associated with an overexpression of various molecular targets; accordingly, various target-specific chemotherapeutic agents have been developed. Inhibition of ERK2, a member of MAPK pathway, is an important target involved in the treatment of both oestrogen receptor-positive and triple-negative breast cancer. Thus, in continuation of our previous work on the ERK2 target, we here report novel inhibitors of this kinase. Out of three lead molecules reported in our previous study, we selected the thiazolidinone-pyrimidine scaffold for further development of small molecule inhibitors of ERK2. Analogues of the lead molecule were docked in the target kinase, followed by molecular dynamic simulations and MM-GBSA calculations. Analogues maintaining key interactions with amino acid residues in the ATP-binding domain of ERK2 were selected and duly synthesized. In vitro biochemical evaluation of these molecules against ERK2 kinase disclosed that two molecules possess significant kinase inhibitory potential with IC50 values ≤ 0.5 µM.

Recent Advances in Nanotherapeutic Interventions for the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD), with impairment of learning and memory as the common clinical manifestations, is one of the most challenging diseases affecting individuals, their families and society as a whole. The fact that its prevalence is escalating rapidly, with the total number of AD patients estimated to reach 115.4 million by 2050, has made the disease a very challenging ailment worldwide. Several biological barriers like the bloodbrain barrier (BBB), drug efflux by P-glycoprotein and the blood-cerebrospinal fluid barrier restrict the delivery of conventional AD drugs to the central nervous system (CNS), thereby limiting their effectiveness. In order to overcome the above physiological barriers, the development of nanomedicines has been extensively explored. The present review provides an insight into the pathophysiology of AD and risk factors associated with AD. Besides, various nanoformulations reported in the literature for the diagnosis and treatments of AD have been classified and summarised. The patented nanoformulations for AD and details of nanoformulations which are in clinical trials are also mentioned. The review would be helpful to researchers and scientific community by providing them with information related to the recent advances in nanointerventions for the diagnosis and treatment of AD, which they can further explore for better management of the disease. However, although the nanotherapeutics for managing AD have been extensively explored, the factors which hinder their commercialisation, the toxicity concern being one of them, need to be addressed so that effective nanotherapeutics for AD can be developed for clinical use.

Induced photolysis of DDT.

Photolysis of mixtures of certain alkyl halides and aromatic amines produces dehalogenation of the halide. These reactions involve a photoinduced charge transfer from the amine to the halide. Photolysis of tritolylamine and carbon tetrachloride produces tritolylaminium chloride. Photolysis of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) and diethylaniline at 3100 angstroms yields 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane (DDD), p,p'-dichlorobenzophenone (DDCO), and hydrogen chloride. Photolysis of DDT does not occur unless an inducer which has a low ionization potential, such as diethylaniline, is present. The DDT-diethylaniline mixture is stable in the dark, and the induced photolysis is not affected by triplet quenchers.

Clinical and angiographic profiles and six months outcomes of smokers with acute ST segment elevation myocardial infarction undergoing primary percutaneous coronary angioplasty.

BACKGROUND: Outcomes of primary percutaneous coronary intervention (PCI) for acute STEMI (ST-segment elevation myocardial infarction) in smokers are expected to be better than non-smokers as for patients of acute STEMI with or without fibrinolytic therapy. OBJECTIVES: This comparative study was designed to evaluate the outcomes of primary PCI in patients with acute STEMI in smokers and non-smokers. Clinical and angiographic profile of the two groups was also compared. METHODS: Over duration of two year, a total of 150 consecutive patients of acute STEMI eligible for primary PCI were enrolled and constituted the two groups [Smokers (n=90), Non-smokers (n=60)] of the study population. There was no difference in procedure in two groups. RESULTS: In the present study of acute STEMI, current smokers were about a decade younger than non-smokers (p value=0.0002), majority were male (98.9% vs 56.6%) were male with a higher prevalence of hypertension and diabetes mellitus (61.67% vs 32.28% and 46.67% vs 14.44%, p=0.001) respectively. Smokers tended to have higher thrombus burden (p=0.06) but less multi vessel disease (p=0.028). Thirty day and six month mortality was non-significantly higher in smokers 4.66% vs 1.33% (p=0.261) and 5.33% vs 2.66% (p=NS) respectively. Rate of quitting smoking among smokers was 80.90% at 6 months. CONCLUSION: The study documents that smokers with acute STEMI have similar outcomes as compared to non smokers with higher thrombus burden and lesser non culprit artery involvement. Smokers present at much younger age emphasizing the role of smoking cessation for prevention of myocardial infarction.

Clinico-epidemiological profile and validation of symptoms and signs of severe illness in young infants (< 60 days) reporting to a district hospital.

OBJECTIVES: To describe the clinical and epidemiological profile of infants less than 2 months of age reporting to a district hospital and to assess the ability of simple clinical symptoms and signs used by health workers to detect severe illness warranting hospital admission. METHODS: It was an observational study done at a general district hospital at Chandigarh, North India. Infants less than 2 months of age presenting to this hospital were enrolled. All infants were first evaluated by an auxiliary nurse midwife (ANM) to record a pre-determined set of symptoms and signs. A pediatrician who was blinded to the findings of the ANM did an independent assessment for severe illness needing urgent hospitalization. RESULTS: A total of 1268 infants were enrolled. Of these, 356 (28%) were below 7 days of age. Overall, regurgitation, vomiting and stool problems (25%) were the most common presenting complaints in the first 2 months of life, followed by jaundice (22%) and respiratory symptoms (15%). 112 (8.8%) infants were classified as having "severe illness requiring urgent hospital management" by the pediatrician. Nearly half (46%) of the admissions were because of jaundice while 17% each were due to sepsis and pneumonia / lower respiratory tract infection (LRTI). A history of not feeding well (OR 14.7, 8.0 and 11.3 in 0-6, 7-27 and 28-59 days age groups, respectively) and a respiratory rate >60/min (OR 21.5, 6.2 and 10.5 in 0-6, 7-27 and 28-59 days age groups, respectively) had significant positive predictive value to predict severe illness (except jaundice) in all the 3 age groups studied. In the second month of life, severe chest in-drawing (OR 4.6) was also a significant predictor. CONCLUSIONS: Simple clinical signs are useful in hands of health worker for identifying neonates with serious illness warranting hospital admission. These will be of use in the further development of clinical algorithms for the national integrated management of childhood illnesses.

Knowledge, attitude and practice about breast cancer and breast self-examination among women seeking out-patient care in a teaching hospital in central India.

BACKGROUND: Breast cancer (BC) continues to be a major cause of morbidity and mortality throughout the world. Early detection of BC and early treatment increases the chance of survival. According to Breast Health Global Initiative guidelines for low and middle income countries, diagnosing BCs early by promoting breast self-awareness; clinical breast examination (CBE) and resource adapted mammographic screening will reduce BC mortality. There is a paucity of data on the knowledge and awareness of BC and self-breast examination in India. We designed this hospital based cross sectional descriptive study to evaluate the current status of knowledge, awareness and practices related to BC and breast self-examination in the female rural population attending a teaching hospital. MATERIALS AND METHODS: We did a random sampling to identify and enroll 360 women and their female relatives. We excluded a participant from the study if she had already undergone a screening mammography or had had a BC. The data was collected by a self-administered questionnaire in vernacular language. RESULTS: Our study population included 360 women with a mean age of 45.81 (±10.9) years. Only 5 (1.38%) females had a family history of BC. A whopping 81% of women did not have any knowledge about BC. All the women thought that CBE by doctors was the only way for screening BC. CONCLUSIONS: We concluded that with the results of this study, it is imperative to increase awareness about BC and its detection methods in the community through health education campaigns. We should have major policy changes to increase future screening programs and health education programs which would have an overall positive impact on reducing the disease burden.

A review of emerging trends in the treatment of tuberculosis.

This review attempts to summarize the information available on emerging trends in the treatment of tuberculosis caused by the bacteria Mycobacterium tuberculosis. Nanostructured biomaterials, liposomes, microparticles and solid lipid nanoparticles have unique physicochemical properties such as particularly small and convenient size, sustained release, great surface area to mass ratio and high reactivity with structure. These properties can be useful in easing the administration of antimicrobial drugs, thereby reducing the number of limitations in long-established antimicrobial therapeutics. In recent years, the encapsulation of antimicrobial drugs in all carrier systems has emerged as an innovative and promising change that increases therapeutic efficiency and reduces undesirable side effects of the drugs.

Drug susceptibility of rapid and slow growing non-tuberculous mycobacteria isolated from symptomatics for pulmonary tuberculosis, Central India.

BACKGROUND: Non-tuberculous mycobacteria (NTM) are emerging as important pathogens. Their treatment also differs from that of Mycobacterium tuberculosis. In India, any datum on them is scarce as species identification and drug susceptibility are not performed in most laboratories. Susceptibility also differs from one geographic area to another, and in our country, there are no data even to guide the clinicians to start treatment empirically. METHODOLOGY: The present study endeavours to generate drug susceptibility data on NTM isolated from sputum samples collected and stored from 6445 symptomatics for pulmonary tuberculosis during a prevalence survey and from specimens received from the hospital. Isolates were not necessarily associated with the disease. Species were identified and antibiotic susceptibility was performed using micro-broth dilution technique as per the standard Clinical and Laboratory Standards Institute guidelines. RESULTS: A total of 65 NTM with 11 species were identified, of which 27 belonged to Mycobacterium fortuitum complex, 14 Mycobacterium gordonae, 9 Mycobacterium avium, 7 Mycobacterium flavescens, 4 Mycobacterium scrofulaceum and one each of others. Sensitivity to amikacin for M. fortuitum was 95.22% (20 out of 21), followed by ciprofloxacin (76.19%) and clarithromycin (71.42%). All the 9 M. avium isolates, 11 of M. gordonae (78.57%), 5 of M. flavescens and 2 of M. scrofulaceum were sensitive to clarithromycin. All NTM were resistant to first-line antitubercular drugs except 8, which were sensitive to streptomycin. CONCLUSIONS: Drug sensitivity of NTM varies from species to species. While amikacin was the best for rapidly growing mycobacteria, clarithromycin was the most active drug against M. avium and other slow growers.

APOA1-75 G to A substitution associated with severe forms of CAD, lower levels of HDL and apoA-I among northern Indians.

Apolipoprotein A-I (APOA1 gene, apoA-I protein) is the major protein for plasma high density lipoprotein (HDL). The relationship of APOA1-75G/A polymorphism with lipid profile and coronary artery disease (CAD) is unclear. Out of 370 individuals initially recruited, 164 angiographically proven CAD patients (>/= 70% stenosis) and 36 individuals with normal coronaries or insignificant CAD (NCAD,

Prevalence of tuberculous lymphadenitis in children in Wardha district, Maharashtra State, India.

SETTING: Rural area of Wardha district, Maharashtra State, Central India. OBJECTIVE: To determine the prevalence of tuberculous lymphadenitis in children aged 0-14 years in the study area and to assess factors that may contribute towards the prevalence. DESIGN: House to house survey of a population of 23,229 in 35 neighbouring villages with 7900 children aged 0-14 years from May 1993 to May 1994 and from March 1995 to February 1996. RESULTS: The prevalence of tuberculous lymphadenitis/1000 children was 4.43. The maximum prevalence was in the 5-9 years age group. The prevalence was 34 times higher in children with positive family history of tuberculosis than in those without a history. There was an association between prevalence and the living standards of the children, with a higher prevalence in families that belonged to an underprivileged social class living in thatched, improvised houses. Multiple cervical lymph nodes >2 cm and with matting and fluctuation were found to be characteristic clinical features. CONCLUSION: The prevalence of peripheral lymphadenopathy was 27.2/1000 children and that of tuberculous lymphadenitis was 4.43/1000. Positive history of contact in the family was a significant epidemiological indicator of tuberculous glands.

Low-density lipoprotein cholesterol estimation by a new formula in Indian population.

BACKGROUND: Estimation of low-density lipoprotein cholesterol is crucial in the management of ischemic heart disease patients. Low-density lipoprotein cholesterol is routinely calculated in laboratories world over by applying Friedewald formula for logistic reasons. We derived a new formula based on multiple regression approach. METHODS: Lipid profiles were done on blood samples of 2008 patients. In initial 1000 patients, low-density lipoprotein cholesterol was estimated by a direct method and also by Friedewald formula. By applying linear regression methods on the data of direct estimation method, a new formula was obtained and the accuracy of this new formula was validated in the next 1008 patients. RESULTS: The mean low-density lipoprotein cholesterol was 116+/-41.5 mg/dl (3.02+/-1.08 mmol/l) measured by direct low-density lipoprotein cholesterol assay and that calculated by Friedewald formula was 119+/-46 mg/dl (3.09+/-1.2 mmol/l) for the initial 1000 patients. Low-density lipoprotein cholesterol measured by direct low-density lipoprotein cholesterol assay and calculated from Friedewald formula showed good correlation (r = 0.88), however, there was minimal overestimation by the Friedewald formula. The correlation improved between direct low-density lipoprotein cholesterol and calculated low-density lipoprotein cholesterol after excluding the patients with triglycerides more than 350 mg/dl (r = 0.92). The mean low-density lipoprotein cholesterol measured by the direct assay and by new formula in the next 1008 patients was 117+/-40 mg/dl (3.04+/-1.04 mmol/l) and 113.7+/-37 mg/dl (2.96+/-0.96 mmol/l), respectively with very good correlation (r = 0.97) between them. CONCLUSIONS: The new formula derived from multiple linear regression analysis appears to be more accurate than Friedewald formula in Indian population.

Pharmacokinetic study of antipyrine in malnourished children.

Plasma half-life and metabolic clearance rate of antipyrine administered intravenously in a dose of 16 mg/kg body weight was studied in 10 children suffering from protein calorie malnutrition and five normal children matched in age and sex. Plasma half-life was increased and metabolic clearance rate was decreased in malnourished children (10.4 hr and 47.1 ml/hr per kg, respectively) in comparison to controls (6.3 hr and 70.1 ml/hr per kg, respectively). This observation indirectly reflects the lowered activity of microsomal oxidative enzyme of liver. Five children were restudied after nutritional rehabilitation of 17 to 25 days. Antipyrine plasma half-life decreased to 6.6 hr and metabolic clearance rate increased to 66.5 ml/hr per kg. These values were similar to those in normal children indicating biological recovery. The drug therapy in children with protein calorie malnutrition requires reconsideration in light of these observations.