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1.  Pentazocine-induced contractures: Dilemma in management 
Indian Journal of Pharmacology  2015;47(4):451-453.
Pentazocine is a commonly used synthetic opioid analgesic for moderate to severe pain secondary to various conditions. Complications of parenteral opioid abuse including localized ulcerations, abscess, indurations, and sclerosis are well-documented. We present a rare case of drug abuse due to pentazocine (Fortwin) in a 32-year-old female, who had severe myogenic contractures of her knee joints.
PMCID: PMC4527072  PMID: 26288482
Contractures; myopathy; pentazocine; pentazocine abuse
2.  Biology & control of Anopheles culicifacies Giles 1901 
Malaria epidemiology is complex due to multiplicity of disease vectors, sibling species complex and variations in bionomical characteristics, vast varied terrain, various ecological determinants. There are six major mosquito vector taxa in India, viz. Anopheles culicifacies, An. fluviatilis, An. stephensi, An. minimus, An. dirus and An. sundaicus. Among these, An. culicifacies is widely distributed and considered the most important vector throughout the plains and forests of India for generating bulk of malaria cases (>60% annually). Major malaria epidemics are caused by An. culicifaices. It is also the vector of tribal malaria except parts of Odisha and Northeastern States of India. An. culicifacies has been the cause of perennial malaria transmission in forests, and over the years penetrated the deforested areas of Northeast. An. culicifacies participates in malaria transmission either alone or along with An. stephensi or An. fluviatilis. The National Vector Borne Disease Control Programme (NVBDCP) spends about 80 per cent malaria control budget annually in the control of An. culicifacies, yet it remains one of the most formidable challenges in India. With recent advances in molecular biology there has been a significant added knowledge in understanding the biology, ecology, genetics and response to interventions, requiring stratification for cost-effective and sustainable malaria control. Research leading to newer interventions that are evidence-based, community oriented and sustainable would be useful in tackling the emerging challenges in malaria control. Current priority areas of research should include in-depth vector biology and control in problem pockets, preparation of malaria-risk maps for focused and selective interventions, monitoring insecticide resistance, cross-border initiative and data sharing, and coordinated control efforts for achieving transmission reduction, and control of drug-resistant malaria. The present review on An. culicifacies provides updated information on vector biology and control outlining thrust areas of research.
PMCID: PMC4510750  PMID: 26139769
Anopheles culicifacies; bionomics distribution; India; insecticide resistance; malaria; sibling species; vector genetics
3.  Genome Sequence of Classical Swine Fever Virus Genotype 1.1 with a Genetic Marker of Attenuation Detected in a Continuous Porcine Cell Line 
Genome Announcements  2015;3(2):e00375-15.
The complete genome sequencing and analysis of a classical swine fever virus (CSFV) detected in a porcine kidney cell line revealed a close relationship with genotype 1.1 viruses circulating in India and China. The presence of consecutive T insertions in the 3′ untranslated region (UTR), as seen in vaccine strains of CSFV, suggested some degree of attenuation.
PMCID: PMC4417697  PMID: 25931601
4.  A reliable and cost effective approach for radiographic monitoring in nutritional rickets 
The British Journal of Radiology  2014;87(1036):20130648.
Radiological scoring is particularly useful in rickets, where pre-treatment radiographical findings can reflect the disease severity and can be used to monitor the improvement. However, there is only a single radiographic scoring system for rickets developed by Thacher and, to the best of our knowledge, no study has evaluated radiographic changes in rickets based on this scoring system apart from the one done by Thacher himself. The main objective of this study is to compare and analyse the pre-treatment and post-treatment radiographic parameters in nutritional rickets with the help of Thacher's scoring technique.
176 patients with nutritional rickets were given a single intramuscular injection of vitamin D (600 000 IU) along with oral calcium (50 mg kg−1) and vitamin D (400 IU per day) until radiological resolution and followed for 1 year. Pre- and post-treatment radiological parameters were compared and analysed statistically based on Thacher's scoring system.
Radiological resolution was complete by 6 months. Time for radiological resolution and initial radiological score were linearly associated on regression analysis. The distal ulna was the last to heal in most cases except when the initial score was 10, when distal femur was the last to heal.
Thacher's scoring system can effectively monitor nutritional rickets. The formula derived through linear regression has prognostic significance.
Advances in knowledge:
The distal femur is a better indicator in radiologically severe rickets and when resolution is delayed. Thacher's scoring is very useful for monitoring of rickets. The formula derived through linear regression can predict the expected time for radiological resolution.
PMCID: PMC4067015  PMID: 24593231
5.  Multiple Phenotypes in Phosphoglucomutase 1 Deficiency 
The New England journal of medicine  2014;370(6):533-542.
Congenital disorders of glycosylation are genetic syndromes that result in impaired glycoprotein production. We evaluated patients who had a novel recessive disorder of glycosylation, with a range of clinical manifestations that included hepatopathy, bifid uvula, malignant hyperthermia, hypogonadotropic hypogonadism, growth retardation, hypoglycemia, myopathy, dilated cardiomyopathy, and cardiac arrest.
Homozygosity mapping followed by whole-exome sequencing was used to identify a mutation in the gene for phosphoglucomutase 1 (PGM1) in two siblings. Sequencing identified additional mutations in 15 other families. Phosphoglucomutase 1 enzyme activity was assayed on cell extracts. Analyses of glycosylation efficiency and quantitative studies of sugar metabolites were performed. Galactose supplementation in fibroblast cultures and dietary supplementation in the patients were studied to determine the effect on glycosylation.
Phosphoglucomutase 1 enzyme activity was markedly diminished in all patients. Mass spectrometry of transferrin showed a loss of complete N-glycans and the presence of truncated glycans lacking galactose. Fibroblasts supplemented with galactose showed restoration of protein glycosylation and no evidence of glycogen accumulation. Dietary supplementation with galactose in six patients resulted in changes suggestive of clinical improvement. A new screening test showed good discrimination between patients and controls.
Phosphoglucomutase 1 deficiency, previously identified as a glycogenosis, is also a congenital disorder of glycosylation. Supplementation with galactose leads to biochemical improvement in indexes of glycosylation in cells and patients, and supplementation with complex carbohydrates stabilizes blood glucose. A new screening test has been developed but has not yet been validated. (Funded by the Netherlands Organization for Scientific Research and others.)
PMCID: PMC4373661  PMID: 24499211
6.  Epidemiological pattern of psoriasis, vitiligo and atopic dermatitis in India: Hospital-based point prevalence 
Indian Dermatology Online Journal  2014;5(Suppl 1):S6-S8.
The knowledge of the prevalence of common dermatoses will be useful for optimum use of valuable resources of the country.
The aim of the study is to determine the pattern and prevalence of psoriasis, vitiligo and atopic dermatitis (AD) in India.
Materials and Methods:
This was a hospital-based study conducted on a single day in one medical college each in four zones of India.
The point prevalence of dermatological cases was 9.25%. The point prevalence of psoriasis, vitiligo and AD were 8%, 9.98% and 6.75% respectively. Chronic plaque type psoriasis was the most common (50%) clinical pattern. The most common site of involvement of psoriasis was the palms. Stable type of vitiligo was common which accounted for 65.21%. Lower lip was involved in 75% of mucosal vitiligo. Lower limbs were the most common site of onset of vitiligo. AD was most prevalent in the first decade (40.7%). Personal history of atopy was present in (59.5%) patients. Dry skin was present in 92.5% of patients.
Our data correlates with previous hospital-based prevalence studies of psoriasis, vitiligo and AD.
PMCID: PMC4252960  PMID: 25506573
Atopic dermatitis; psoriasis; vitiligo
7.  Genetic architecture underlying morning and evening circadian phenotypes in fruit flies Drosophila melanogaster 
Heredity  2013;111(4):265-274.
Circadian rhythms are perhaps among the genetically best characterized behaviours. Several mutations with drastic effects on circadian processes have been identified and models developed to explain how clock genes and their products generate self-sustained oscillations. Although natural variations in circadian phenotypes have been studied extensively, the genetic basis of such adaptive variations remains largely unknown. Here we report the results of a preliminary genetic analysis of adaptive divergence of circadian phenotypes in populations of fruit flies Drosophila melanogaster. Two sets of populations, ‘early' and ‘late', were created in a long-term laboratory selection for morning and evening emergence, with four independent replicates each. Over the course of ∼55 generations, the early flies evolved increased morning emergence and a shorter circadian period, whereas late flies evolved increased evening emergence and longer period. To examine the genetic basis of circadian phenotypes, we set up crosses between early and late flies, and monitored emergence and activity/rest rhythms in the F1, backcrossed and F2 progeny. Our analysis suggests that the genetic basis of divergent circadian phenotypes in early and late stocks is primarily autosomal. Line-cross analysis revealed that additive and non-additive genetic effects contribute to the divergence of circadian phenotypes in early and late flies.
PMCID: PMC3807266  PMID: 23612693
Drosophila; circadian; adult emergence; activity/rest; genetic bases
8.  Escherichia coli O157:H7 Lacking the qseBC-Encoded Quorum-Sensing System Outcompetes the Parental Strain in Colonization of Cattle Intestines 
The qseBC-encoded quorum-sensing system regulates the motility of Escherichia coli O157:H7 in response to bacterial autoinducer 3 (AI-3) and the mammalian stress hormones epinephrine (E) and norepinephrine (NE). The qseC gene encodes a sensory kinase that autophosphorylates in response to AI-3, E, or NE and subsequently phosphorylates its cognate response regulator QseB. In the absence of QseC, QseB downregulates bacterial motility and virulence in animal models. In this study, we found that 8- to 10-month-old calves orally inoculated with a mixture of E. coli O157:H7 and its isogenic qseBC mutant showed significantly higher fecal shedding of the qseBC mutant. In vitro analysis revealed similar growth profiles and motilities of the qseBC mutant and the parental strain in the presence or absence of NE. The magnitudes of the response to NE and expression of flagellar genes flhD and fliC were also similar for the qseBC mutant and the parental strain. The expression of ler (a positive regulator of the locus of enterocyte effacement [LEE]), the ler-regulated espA gene, and the csgA gene (encoding curli fimbriae) was increased in the qseBC mutant compared to the parental strain. On the other hand, growth, motility, and transcription of flhD, fliC, ler, espA, and csgA were significantly reduced in the qseBC mutant complemented with a plasmid-cloned copy of the qseBC genes. Thus, in vitro motility and gene expression data indicate that the near-parental level of motility, ability to respond to NE, and enhanced expression of LEE and curli genes might in part be responsible for increased colonization and fecal shedding of the qseBC mutant in calves.
PMCID: PMC3957642  PMID: 24413602
9.  Mortality profile of patients with traumatic spinal injuries at a level I trauma care centre in India 
Background & objectives:
There is no national spinal trauma registry available in India at present and the research on epidemiology of these injuries is also very limited. The purpose of this study was to describe the mortality profile of patients with spinal injuries brought to a level I trauma centre in India, and to understand the predictive factors which identify patients at an increased risk of spinal trauma mortality.
Retrospective data were collected from computerized patients records and autopsy reports maintained in the department of Forensic Medicine. All the cases with spinal injuries whether in isolation or as a part of polytrauma were reviewed. A total of 341 such cases were identified between January 2008 to December 2011. The demographic data, type of trauma, duration of survival, body areas involved, level of spinal injury and associated injuries if any, were recorded.
There were 288 (84.45%) males and 53 (15.55%) females. Most victims (73%) were between 25 and 64 yr of age, followed by young adults between 16 and 24 yr (19.35%). Male: female ratio was 5.4:1. Fifty five per cent cases had spinal injuries in isolation. Injury to the cervical spine occurred in 259 (75.95%) patients, thoracic spine in 56 (16.42%) and thoraco-lumbar spine in 26 (7.62%) patients. The commonest cause of injury was high energy falls (44.28%), followed by road traffic accidents (41.93%). The majority of deaths (51.6%) occurred in the phase IV (secondary to tertiary complications of trauma, i.e. >1 wk). Forty patients died in phase I (brought dead or surviving <3 h), 55 in phase II (>3 to 24 h) and 70 in phase III (> 24 h to 7 days).
Interpretation & conclusions:
Our data suggest that there is an urgent need to take steps to prevent major injuries, strengthen the pre-hospital care, transportation network, treatment in specialized trauma care units and to improve injury surveillance and the quality of data collected which can guide prevention efforts to avoid loss of young active lives.
PMCID: PMC4181158  PMID: 25222776
Injury prevention; mortality patterns; post-traumatic; spinal injuries
10.  From Childhood Migraine Headache to Pheochromocytoma 
Case Reports in Endocrinology  2014;2014:746723.
Pheochromocytoma may have multiple clinical manifestations including paroxysmal hypertension, tachycardia, sweating, nausea, and headache (Phillips et al., 2002). Migraine has some of the manifestations seen with pheochromocytoma. We describe a patient who had a history of migraine headaches since childhood and was found to have pheochromocytoma. Resection of her tumor significantly improved her headache. The diagnoses of pheochromocytoma subsequently lead to diagnosing her with medullary thyroid cancer (MTC) and multiple endocrine neoplasia type 2A (MEN-2A).
PMCID: PMC4058218  PMID: 24977088
11.  Correlation of serum phosphate with carotid intimal-medial thickness in chronic kidney disease patients 
Indian Journal of Nephrology  2014;24(1):15-19.
While increased serum phosphate concentration is a significant risk factor for vascular calcification, it is unclear whether serum phosphate is also a risk factor for increased arterial wall thickness in chronic kidney disease (CKD) patients. Using B-mode ultrasonography, we examined carotid intimal-medial thickness (CIMT) of CKD patients and analyzed risk factors for increased IMT with regard to the effect of serum phosphate. One hundred patients were enrolled (73 patients without diabetes, 27 patients with diabetes; 57 men, 43 women; age, 46.2 ± 15.3 years). CIMT of patients with diabetes was significantly greater than that of patients without diabetes (0.78 ± 0.250 versus 0.66 ± 0.178 mm; P < 0.0001). For the group of all patients, CIMT correlated strongly and significantly with serum phosphate (r = 0.911; P < 0.001). In multiple regression analysis serum phosphate level (β = 0.356; <0.0001) was found to be a significant independent risk factor for increased CIMT, in addition to other independent risk factors, including advanced age, higher systolic blood pressure, urinary albumin and the presence of diabetes (R2 = 0.956; P < 0.00001). In conclusion, high serum phosphate level is a significant and independent factor associated with advanced arteriosclerosis in CKD patients with and without diabetes in addition to advanced age.
PMCID: PMC3927184  PMID: 24574625
Carotid intimal-medial thickness; chronic kidney disease; diabetes; phosphate
12.  An improved plant regeneration and Agrobacterium - mediated transformation of red pepper (Capsicum annuum L.) 
Capsicum annuum (red pepper) is an important spice cum vegetable crop in tropical and subtropical countries. Here, we report an effective and reproducible auxin free regeneration method for six different red pepper cultivars (ACA-10, Kashi Anmol, LCA-235, PBC-535, Pusa Jwala and Supper) using hypocotyl explants and an efficient Agrobacterium-mediated transformation protocol. The explants (hypocotyls, cotyledonary leaves and leaf discs) collected from axenic seedlings of six red pepper cultivars were cultured on either hormone free MS medium or MS medium supplemented with BAP alone or in combination with IAA. Inclusion of IAA in the regeneration medium resulted in callus formation at the cut ends of explants, formation of rosette leaves and ill defined shoot buds. Regeneration of shoot buds could be achieved from hypocotyls grown in MS medium supplemented with different concentrations of BAP unlike other explants which failed to respond. Incorporation of GA3 in shoot elongation medium at 0.5 mg/l concentration enhanced the elongation in two cultivars, LCA-235 and Supper, while other cultivars showed no significant response. Chilli cultivar, Pusa Jwala was transformed with βC1 ORF of satellite DNA β molecule associated with Chilli leaf curl Joydebpur virus through Agrobacterium tumefaciens. Transgene integration in putative transformants was confirmed by PCR and Southern hybridization analysis.
PMCID: PMC3550559  PMID: 24082498
Capsicum annuum; Plant regeneration; Agrobacterium tumefaciens; Genetic transformation; Transgenic plants; Chilli leaf curl virus
13.  Bilateral idiopathic orbital inflammatory syndrome with grossly elevated creatinine kinase levels 
Eye  2011;26(4):613-614.
PMCID: PMC3325564  PMID: 22193876
14.  Biochemical Indicator of Sickle Cell Disease: Preliminary Report from India 
Blood biochemistry has significant effect on pathophysiology of human body. Recently few studies found the association of biochemical abnormalities in sickle cell patients. Sickle cell disease showed clinical variability where African ancestors have severe phenotype than Indian sicklers. Our aim was to evaluate the biochemicals in sickle cell patients and their effect on severity. Here we present the comparative biochemical levels in sickle cell patients as well as controls. Sickle cell patients diagnosed by HPLC and biochemical analysis done by Beckman-auto analyzer. T test applied for statistical analysis. Result showed the renal abnormality lesser in patients and related biochemical within the normal range and statistically not significant. Electrolytes, hepatic enzymes, alkaline phosphatase and glucose were elevated and statistically significant (P value <0.05). Observation of the study concludes the biochemical abnormality play a significant role in sickle cell patient’s physiopathology and can be used to management of the disease.
PMCID: PMC3358379  PMID: 23542695
Sickle cell anaemia; Biochemical; High performance liquid chromatography
15.  Comparison of esthetic outcome after extraction or non-extraction orthodontic treatment in class II division 1 malocclusion patients 
Contemporary Clinical Dentistry  2013;4(2):206-212.
The extraction of premolars as a practical form of orthodontic therapy has been accepted for many years, but there remains a controversy regarding the effect of premolar extraction to improve esthetics as well as dentoskeletal relationship. The esthetic impact of the soft-tissue profile might play a major role in deciding on premolar extraction or non-extraction treatment, particularly in borderline patients. This cephalometric study was undertaken to compare the post-treatment soft-tissue profiles of successfully managed Class II, Division 1 malocclusions treated with either all first premolar extractions or treatment with a non-extraction therapy.
Materials and Methods:
The sample consisted of 100 post-pubertal female patients of Class II Division I malocclusion. Group 1, treated with four first premolar extractions, consisted of 50 female patients with a mean age of 14 years 1 month. Group 2, treated without extractions, consisted of 50 patients with a mean age of 13 years 5 months. Pre-treatment and post-treatment lateral cephalometric radiographs were evaluated. The pre-treatment to post-treatment stage comparison and the intergroup comparison of the treatment changes were conducted between extraction and non-extraction groups of Class II malocclusion samples with t-tests.
The soft-tissue facial profiles of the extraction and non-extraction samples were the same following active treatment except for a more retruded lower lip and a more pronounced lower labial sulcus in those patients subjected to extraction.
The extraction or non-extraction decision, if based on sound diagnostic criteria, seems to have no systematic detrimental effects on the facial profile.
PMCID: PMC3757883  PMID: 24015010
Dentoskeletal changes; extraction-non-extraction patients; standard edgewise mechanics; soft-tissue profile
16.  Metabolite Profiling in the Pursuit of Biomarkers for IVF Outcome: The Case for Metabolomics Studies 
Background. This paper presents the literature on biomarkers of in vitro fertilisation (IVF) outcome, demonstrating the progression of these studies towards metabolite profiling, specifically metabolomics. The need for more, and improved, metabolomics studies in the field of assisted conception is discussed. Methods. Searches were performed on ISI Web of Knowledge SM for literature associated with biomarkers of oocyte and embryo quality, and biomarkers of IVF outcome in embryo culture medium, follicular fluid (FF), and blood plasma in female mammals. Results. Metabolomics in the field of female reproduction is still in its infancy. Metabolomics investigations of embryo culture medium for embryo selection have been the most common, but only within the last five years. Only in 2012 has the first metabolomics investigation of FF for biomarkers of oocyte quality been reported. The only metabolomics studies of human blood plasma in this context have been aimed at identifying women with polycystic ovary syndrome (PCOS). Conclusions. Metabolomics is becoming more established in the field of assisted conception, but the studies performed so far have been preliminary and not all potential applications have yet been explored. With further improved metabolomics studies, the possibility of identifying a method for predicting IVF outcome may become a reality.
PMCID: PMC4334075  PMID: 25763388
17.  Battling malaria iceberg incorporating strategic reforms in achieving Millennium Development Goals & malaria elimination in India 
Malaria control in India has occupied high priority in health sector consuming major resources of the Central and State governments. Several new initiatives were launched from time to time supported by foreign aids but malaria situation has remained static and worsened in years of good rainfall. At times malaria relented temporarily but returned with vengeance at the local, regional and national level, becoming more resilient by acquiring resistance in the vectors and the parasites. National developments to improve the economy, without health impact assessment, have had adverse consequences by providing enormous breeding grounds for the vectors that have become refractory to interventions. As a result, malaria prospers and its control is in dilemma, as finding additional resources is becoming difficult with the ongoing financial crisis. Endemic countries must contribute to make up the needed resources, if malaria is to be contained. Malaria control requires long term planning, one that will reduce receptivity and vulnerability, and uninterrupted financial support for sustained interventions. While this seems to be a far cry, the environment is becoming more receptive for vectors, and epidemics visit the country diverting major resources in their containment, e.g. malaria, dengue and dengue haemorrhagic fevers, and Chikungunya virus infection. In the last six decades malaria has taken deep roots and diversified into various ecotypes, the control of these ecotypes requires local knowledge about the vectors and the parasites. In this review we outline the historical account of malaria and methods of control that have lifted the national economy in many countries. While battles against malaria should continue at the local level, there is a need for large scale environmental improvement. Global Fund for AIDS, Tuberculosis and Malaria has provided huge funds for malaria control worldwide touching US$ 2 billion in 2011. Unfortunately it is likely to decline to US$ 1.5 billion in the coming years against the annual requirement of US$ 5 billion. While appreciating the foreign assistance, we wish to highlight the fact that unless we have internal strength of resources and manpower, sustained battles against malaria may face serious problems in achieving the final goal of malaria elimination.
PMCID: PMC3612321  PMID: 23391787
Drug resistance; malaria elimination; malaria profile; malaria vectors; MDG; MPO; urban malaria scheme
18.  Editorial 
PMCID: PMC3235385  PMID: 23024486
19.  Correlating Levels of Type III Secretion and Secreted Proteins with Fecal Shedding of Escherichia coli O157:H7 in Cattle 
Infection and Immunity  2012;80(4):1333-1342.
The locus of enterocyte effacement (LEE) of Escherichia coli O157:H7 (O157) encodes a type III secretion system (T3SS) for secreting LEE-encoded and non-LEE-encoded virulence proteins that promote the adherence of O157 to intestinal epithelial cells and the persistence of this food-borne human pathogen in bovine intestines. In this study, we compared hha sepB and hha mutants of O157 for LEE transcription, T3SS activity, adherence to HEp-2 cells, persistence in bovine intestines, and the ability to induce changes in the expression of proinflammatory cytokines. LEE transcription was upregulated in the hha sepB and hha mutant strains compared to that in the wild-type strain, but the secretion of virulence proteins in the hha sepB mutant was severely compromised. This reduced secretion resulted in reduced adherence of the hha sepB mutant to Hep-2 cells, correlating with a significantly shorter duration and lower magnitude of fecal shedding in feces of weaned (n = 4 per group) calves inoculated with this mutant strain. The levels of LEE transcription, T3SS activity, and adherence to HEp-2 cells were much lower in the wild-type strain than in the hha mutant, but no significant differences were observed in the duration or the magnitude of fecal shedding in calves inoculated with these strains. Examination of the rectoanal junction (RAJ) tissues from three groups of calves showed no adherent O157 bacteria and similar proinflammatory cytokine gene expression, irrespective of the inoculated strain, with the exception that interleukin-1β was upregulated in calves inoculated with the hha sepB mutant. These results indicate that the T3SS is essential for intestinal colonization and prolonged shedding, but increased secretion of virulence proteins did not enhance the duration and magnitude of fecal shedding of O157 in cattle or have any significant impact on the cytokine gene expression in RAJ tissue compared with that in small intestinal tissue from the same calves.
PMCID: PMC3318423  PMID: 22252878
24.  Novel Trichomonacidal Spermicides▿†‡ 
Metronidazole, the U.S. Food and Drug Administration-approved drug against trichomoniasis, is nonspermicidal and thus cannot offer pregnancy protection when used vaginally. Furthermore, increasing resistance of Trichomonas vaginalis to 5-nitro-imidazoles is a cause for serious concern. On the other hand, the vaginal spermicide nonoxynol-9 (N-9) does not protect against sexually transmitted diseases and HIV in clinical situations but may in fact increase their incidence due to its nonspecific, surfactant action. We therefore designed dually active, nonsurfactant molecules that were capable of killing Trichomonas vaginalis (both metronidazole-susceptible and -resistant strains) and irreversibly inactivating 100% human sperm at doses that were noncytotoxic to human cervical epithelial (HeLa) cells and vaginal microflora (lactobacilli) in vitro. Anaerobic energy metabolism, cell motility, and defense against reactive oxygen species, which are key to survival of both sperm and Trichomonas in the host after intravaginal inoculation, depend crucially on availability of free thiols. Consequently, molecules were designed with carbodithioic acid moiety as the major pharmacophore, and chemical variations were incorporated to provide high excess of reactive thiols for interacting with accessible thiols on sperm and Trichomonas. We report here the in vitro activities, structure-activity relationships, and safety profiles of these spermicidal antitrichomonas agents, the most promising of which was more effective than N-9 (the OTC spermicide) in inactivating human sperm and more efficacious than metronidazole in killing Trichomonas vaginalis (including metronidazole-resistant strain). It also significantly reduced the available free thiols on human sperm and inhibited the cytoadherence of Trichomonas on HeLa cells. Experimentally in vitro, the new compounds appeared to be safer than N-9 for vaginal use.
PMCID: PMC3165359  PMID: 21709091
25.  Association between -1486 T>C and +1174 G>A single nucleotide polymorphisms in TLR9 gene and severity of lupus nephritis 
Indian Journal of Nephrology  2012;22(2):125-129.
Signaling through Toll-like receptor-9 (TLR9), a mediator of innate immune responses, could have a role in the pathogenesis of systemic lupus erythematosus (SLE). Some studies have shown an association between polymorphisms in the TLR9 gene and disease manifestations. We investigated whether two single nucleotide polymorphisms (-1486 T>C and +1174 G>A) in the TLR9 gene are associated with the risk of renal involvement in SLE. DNA samples from 112 SLE patients (62 with lupus nephritis) and 100 healthy controls were obtained. TLR9 polymorphisms (-1486 T>C and +1174 G>A) were analyzed by polymerase chain reaction–restriction fragment length polymorphism. Genotype and allelic frequencies were compared between lupus patients and healthy controls. Clinical and laboratory manifestations and activity scores on renal biopsy of patients with lupus nephritis were compared between various genotypes. There was no difference in the frequency of genotype or allele distribution at either of the two loci between lupus patients and controls and in lupus patients with or without nephritis. Patients with CC/CT genotype at the -1486 position had higher serum creatinine (P = 0.03) and Austin activity scores (P = 0.015). Patients with AA/AG genotype at +1174 position showed higher serum creatinine (P = 0.04), proteinuria (P = 0.011), anti-dsDNA titers (P < 0.001) and Austin activity scores (P = 0.003) than the GG genotype. Variations at the -1486 and +1174 positions of TLR9 gene are not associated with increased risk of SLE or that of kidney involvement in North Indians. CC/CT genotypes at -1486 and AA/AG at +1174 positions are associated with more severe kidney disease at presentation.
PMCID: PMC3391810  PMID: 22787315
Genetics; lupus nephritis; systemic lupus erythematosus; toll-like receptor

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