A micro-costing analysis of nutritional support for persons with TB and their families in India.

Undernutrition is the leading risk factor for TB infection and death in India. We undertook a micro-costing analysis of a nutritional intervention for household contacts of people living with TB in Puducherry, India. We found that the total 6-month food cost for a family of four was USD4/day. We also identified several alternative regimens and cost-lowering strategies to encourage wider adoption of nutritional supplementation as a public health tool.

La sous-nutrition est le principal facteur de risque d'infection et de décès dus à la TB en Inde. Nous avons entrepris une analyse de micro-coût d'une intervention nutritionnelle destinée aux contacts familiaux des personnes atteintes de la TB à Puducherry, en Inde. Nous avons constaté que le coût total de la nourriture pendant 6 mois pour une famille de quatre personnes était de 4 USD par jour. Nous avons également identifié plusieurs régimes alternatifs et stratégies de réduction des coûts pour encourager une adoption plus large de la supplémentation nutritionnelle en tant qu'outil de santé publique.

Laser-Assisted Frenectomy Followed by Post-Operative Tongue Exercises in Ankyloglossia: A Report of Two Cases.

Ankyloglossia, commonly known as tongue-tie, is a developmental abnormality that may interfere in speech and articulation of lingual and sibilant sounds, due to the abnormal lingual frenal attachment. Lingual frenectomy severs the tie, however in adolescents and young adults, kinesthetic awareness, that is, the senses of position and movement of the tongue, needs to be increased. In such a scenario, tongue exercises lend a helping hand. Here, we discuss the benefits of this combined treatment modality in two cases diagnosed with ankyloglossia.

How genetic variation was analyzed in phenytoin-induced gingival enlargement using single-nucleotide polymorphism of candidate gene CYP2C9?

BACKGROUND: Phenytoin-induced gingival overgrowth is an adverse drug reaction affecting few individuals, on phenytoin therapy for its antiepileptic effect. Analysis of genetic variation of CYP2C9*2 gene was done to identify the action of metabolic enzyme cytochrome P 450 on this drug. The main background of this publication is a quick review about one of the molecular techniques used to identify the single-nucleotide polymorphism (SNP) using polymerase chain reaction coupled with restriction fragment length polymorphism (PCR-RFLP). MATERIALS AND METHODS: Deoxyribonucleic acid (DNA) was extracted from 5 ml of venous blood withdrawn from the individual, who had gingival overgrowth following phenytoin therapy. DNA was isolated, using the phenol-chloroform method. Isolated DNA was used for SNP analysis of CYP2C9*2 presentation. The basic procedure used for SNP analysis in our case was PCR-RFLP. RESULTS: Genetic variation of CYP2C9*2 in our case was homomutant. CONCLUSION: The etiology of phenytoin-induced gingival overgrowth is always an enigma, but it is now becoming clearer that a multifactorial role may be involved in the cause. One of the factors analyzed was polymorphism of CYP2C9*2 gene and it was found to be homomutant in our case. Adverse drug reaction can be minimized, by either reducing the drug dosage or drug substitution. However, larger scale genome-wide study has to be carried out to confirm one of the etiopathogenesis as mutation of the CYP2C9 gene, in phenytoin-induced gingival overgrowth.

Antifilarial activity of azadirachtin fuelled through reactive oxygen species induced apoptosis: a thorough molecular study on Setaria cervi.

Efficacious therapeutic strategies against lymphatic filariasis are always sought after. However, natural products are a promising resource for developing effective antifilarial agents. Azadirachtin, a significant tetranortriterpenoid phytocompound found in Azadirachta indica, was evaluated in vitro for antifilarial potential against the filarial parasite Setaria cervi. Dye exclusion and MTT assay confirmed the antifilarial potential of azadirachtin against S. cervi with a median lethal dose (LC50) of 6.28 µg/ml for microfilariae (mf), and 9.55 µg/ml for adult parasites. Morphological aberrations were prominent in the histological sections of the azadirachtin-exposed parasites. Moreover, alterations in the reactive oxygen species (ROS) parameters in treated parasites were evident. Induction of apoptosis in treated parasites was confirmed by DNA laddering, acridine orange (AO)/ethidium bromide (EtBr) double staining and in situ DNA fragmentation. The downregulation of anti-apoptotic CED-9 and upregulation of proapoptotic EGL-1, CED-4 and CED-3 at both the transcription and translation levels confirmed apoptosis execution at the molecular level. Changes in the gene expressions of nuc-1, cps-6 and crn-1 further clarified the molecular cause of DNA degradation. Furthermore, azadirachtin was found to be non-toxic in both in vitro and in vivo toxicity analyses. Therefore, the experimental evidence detailed the pharmacological effectiveness of azadirachtin as a possible therapeutic agent against filariasis.

Exploring the homolog of a novel proinflammatory microfilarial sheath protein (MfP) of Wuchereria bancrofti in the adult-stage bovine filarial parasite Setaria cervi.

A novel microfilarial sheath protein (MfP) of the human filarial parasite Wuchereria bancrofti and its proinflammatory activity on host macrophages were identified recently. MfP is a homolog of the nematode bestrophin-9 superfamily that acts as a ligand of macrophage Toll-like receptor 4 (TLR4) to induce inflammation through NF-κB activation. Therefore, the presence and functional implication of this novel protein in adult-stage parasites were open questions to answer. In this study, the bovine filarial parasite Setaria cervi was used to simulate adult W. bancrofti. We detected the presence of MfP in adult-stage S. cervi through clear immunological cross-reactivity and immunolocalization employing an anti-MfP antibody developed in mice. Therefore, our findings put forward S. cervi as a cost-effective source of immunodominant filarial antigen MfP to simulate its future utilization in the immunotherapeutic intervention of lymphatic filariasis.

Magnetic resonance imaging findings in brain resulting from high-voltage electrical shock injury of the scalp.

We report a case of high-voltage electrical injury to scalp, focusing on the magnetic resonance imaging (MRI) findings in brain. A 51-year-old male suffered burns to the right side of scalp and loss of consciousness following electric shock. Brain abnormalities were detected on MRI taken 4 days after the insult. Right parietal lobe neuroparenchyma beneath the scalp burn defect demonstrated homogeneous hypointensity on T1-weighted MR images, while T2-weighted images depicted hyperintensity mainly in white matter forming finger-like projections. Follow-up MRI showed that the abnormality had disappeared, indicating that the cerebral edema was reversible.

Radiation dose metrics in multidetector computed tomography examinations: A multicentre retrospective study from seven tertiary care hospitals in Kerala, South India.

BACKGROUND: Presently, computed tomography (CT) is the most important source of medical radiation exposure. CT radiation doses vary considerably across institutions depending on the protocol and make of equipment. India does not yet have national or region-specific CT diagnostic reference levels. AIM: To evaluate radiation doses of consecutive multidetector CT (MDCT) examinations based on anatomic region, performed in 1 month, collected simultaneously from seven tertiary care hospitals in Kerala. SETTINGS AND DESIGN: Descriptive study. MATERIALS AND METHODS: We collected the CT radiation dose data of examinations from the seven collaborating tertiary care hospitals in Kerala, performed with MDCT scanners of five different makes. The data included anatomic region, number of phases, CT dose index (CTDIvol), dose-length product (DLP), and effective dose (ED) of each examinations and patient demographic data. STATISTICAL ANALYSIS: We calculated the 25th, 50th, and 75th percentiles of the CTDIvol, DLP, and ED according to anatomic region. We made descriptive comparisons of these results with corresponding data from other countries. RESULTS: Of 3553 patients, head was the most frequently performed examination (60%), followed by abdomen (19%). For single-phase head examinations, 75th percentile of CTDIvol was 68.1 mGy, DLP 1120 mGy-cm, and ED 2.1 mSv. The 75th percentiles of CTDIvol, DLP, and ED for single-phase abdomen examinations were 10.6, 509.3, and 7.7, and multiphase examinations were 14.6, 2666.9, and 40.8; single-phase chest examinations were 23.4, 916.7, and 13.38, and multiphase examinations were 19.9, 1737.6, and 25.36; single-phase neck were 24.9, 733.6, and 3.814, and multiphase neck were 24.9, 2076, and 10.79, respectively. CONCLUSION: This summary CT radiation dose data of most frequently performed anatomical regions could provide a starting point for institutional analysis of CT radiation doses, which in turn leads to meaningful optimization of CT.

Allele-specific polymerase chain reaction for the detection of single nucleotide polymorphism in amlodipine-induced gingival enlargement.

WHAT IS KNOWN AND OBJECTIVE: Studies indicate that there is an increased serum concentration of amlodipine (a calcium channel blocker used to treat hypertension and angina) in patients having mutant multidrug resistance 1 (MDR1) gene. Hence, genetic factors may play a very significant role in amlodipine-induced complications including gingival enlargement. CASE DESCRIPTION: Three patients with amlodipine-induced gingival enlargement showed improvement following drug substitution of amlodipine with enalapril (an angiotensin-converting enzyme inhibitor) and non-invasive periodontal therapy. Using allele-specific polymerase chain reaction, single nucleotide polymorphism of MDR1 gene of heterozygous mutant type (CT genotype) was identified in all three cases. WHAT IS NEW AND CONCLUSION: Drug-induced complications can potentially be a result of genetic factors, in combination with various local and systemic factors. Identifying genetic polymorphisms early might help predict adverse reactions and determine prognosis.

Surface proteins of Setaria cervi induce inflammation in macrophage through Toll-like receptor 4 (TLR4)-mediated signalling pathway.

Lymphatic filariasis is a vectorborne parasitic disease that results in morbidities, disabilities and socio-economic loss each year globally. Inflammatory consequences associated with any form of filariasis have drawn special attention. However, the molecular insight behind the inflammation of host macrophage (MФ) is considered as one of the shaded areas in filarial research. Herein, major emphasis was given to study the signalling pathway of MФ inflammation induced by surface proteins (SPs) of filarial parasite through in vitro and in vivo approaches. Twenty-four hours of in vitro stimulation of Raw MФs with endotoxin-free SPs of Setaria cervi resulted in the secretion of pro-inflammatory cytokines (TNF-α and IL-1ß) that revealed induction of inflammation, which was found to be elicited from classical NF-кB activation. Moreover, this NF-кB activation was found to be signalled from TLR4 and mediated by the downstream signalling intermediates, viz. MyD88, pTAK1 and NEMO. In vivo studies in adult Wistar rats, experimentally injected with SPs, clearly supported the outcomes of in vitro experiments by showing higher degree of inflammation rather classical activation of the peritoneal MФs. Therefore, SPs from S. cervi cuticle could be responsible for the induction of pro-inflammatory response in MФ, which appears to be propagated through TLR4-NF-кB route.

An undiagnosed case of acute myeloid leukemia.

Leukemia is a neoplastic disease characterized by an excessive proliferation of immature white blood cells and their precursors. Oral lesions may be the presenting feature of acute leukemia, which can be rapidly fatal if left untreated. Although many cases of gingival enlargement in patients with acute myeloid leukemia's have been reported in the literature, cases diagnosed by the oral manifestations in India are very few. This report describes the case of a 43-year-old female who presented with gingival bleeding and gingival enlargement. Within a month she developed signs and symptoms of systemic disease such as, and splenomegaly, and upon further investigation, she was diagnosed with acute myeloid leukemia to which she succumbed within 10 days after diagnosis. The need for early diagnosis and referral of this fatal disease are also underline.

Procedures to view aberrations--a travel from protein to gene: literature review.

The diagnosis of any pathology is fundamentally based on the microscopic structure of cells and tissues and this remains as the standard by which all other diagnostic tests are measured. In this era, the pathologists are relying on the examination of tissue section stained by histochemical means and it is supported by the advanced immunological, biochemical and molecular techniques. This review will provide the information about one of the way that can be followed to unravel the molecular mechanism in spotting the disease process. Technologies used to study the cellular process are same for the normal and the abnormal cell. Experimental strategy briefed here is also applicable for both. The cellular process can be studied either from protein to gene or from gene to protein. Earlier days biochemical analysis (isolation of protein, protein sequencing) was separate and genetic analysis (genomic mapping) was separate. But now with advent of recombinant DNA technology it is possible to have a link between the biochemical and genetic analysis. Intermediary step of development of oligonucleotide synthesis, complementary DNA probe and cloning has revolutionized the research process. Identified gene can be compared with the normal gene by comparative genomics or expressed proteins by expression proteomics.

An unusual clinical presentation of gingival melanoacanthoma.

Gingival melanoacanthoma is a rare, benign pigmented lesion characterized clinically by sudden onset and rapid growth of a macular brown black lesion and histologically by acanthosis of superficial epithelium and proliferation of dendritic melanocytes. This article reports a previously undescribed case of pigmented unilateral diffuse gingival enlargement, which on histopathological examination proved to be melanoacanthoma. Intraoral examination revealed pigmented unilateral diffuse gingival enlargement in relation to second and third quadrants buccally, palatally/lingually. Based on these clinical findings, gingivectomy was performed and the excised tissue was sent for biopsy. Microscopic examination revealed acanthotic and parakeratotic surface epithelium with dendritic melanocytes distributed in basal and suprabasal layers of the epithelium. 1 year follow-up recall revealed no recurrence of lesion at the surgical sites. Our patient exhibits an unusual clinical presentation of melanoacanthoma of gingiva. Pigmented gingival overgrowth of recent origin and without any etiologic factors warrants histopathologic examination.

Cytochrome P450 2C9 gene polymorphism in phenytoin induced gingival enlargement: A case report.

Gingival enlargement comprises any clinical condition in which an increase in the size of the gingiva is observed. Among the drugs that induce gingival enlargement, the antiepileptic agent phenytoin has been widely related to this condition. The Cytochrome P450(CYP) superfamily is the most commonly involved enzymes in metabolism of drugs. Common coding region CYP variants that affects drug elimination and response has been studied in great detail. Pharmacogenetic influences on drug metabolism have been widely reviewed and gene polymorphism of cytochrome P450 2C9 appeared to be responsible for much of the interindividual variability on drug elimination. Genetic variation in the CYP2C9 gene can affect metabolism, leading to altered phenotypes. Individuals with poor metaboliser alleles of CYP2C9 gene were shown to have a reduced metabolism of phenytoin compared with wild-type alleles. Thus identification of patients genotype prior to anti-epileptic drug administration could potentially prevent higher serum drug concentrations leading to adverse side effects such as gingival enlargement. This case report addresses the influence of CYP2C9 genetic polymorphism on Phenytoin drug metabolism thereby causing gingival enlargement.

Albendazole induces apoptosis in adults and microfilariae of Setaria cervi.

Setaria cervi, a filarial nematode of cattle, inhabits in the peritoneal cavity and has been used as a suitable model for screening antifilarial agents. Albendazole (ABZ), a tubulin-disrupting benzimidazole (BZ) and a potent microfilaricide binds to ß-tubulin, is causing structural impairment of cytoskeleton and worm death. Our present study has revealed that exposure of microfilaria (Mf) and adult to gradually increasing concentration of ABZ leads to a dose-dependent gradual impairment of their motility followed by early death in vitro. We found extreme cellular disturbances in ABZ-treated worms characterized by nucleosomal DNA laddering and chromatin condensation. However, in the treated Mf no nucleosomal DNA laddering was found although presence of TUNEL reactive DNA was evident, thus indicating an apoptotic pathway independent of DNA fragmentation. We present data from molecular studies to provide evidence for ABZ-induced apoptosis in Mf and adult worms of S. cervi.

Improved efficacy of tetracycline by acaciasides on Dirofilaria immitis.

The discovery of Wolbachia, a bacterial endosymbiont that occurs in the filarial parasite and its sensitivity to tetracycline, has fostered a new initiative in the development of suitable antifilarial drugs. The present study is an attempt to investigate whether adding acaciasides (saponins from Acacia auriculiformis) to the standard dose of tetracycline would further improve the efficacy of tetracycline treatment against Dirofilaria immitis microfilariae in vivo. Treatment of microfilaremic adult dogs (body weight range 8-12 kg) with tetracycline at 10 mg/kg/day for 40 days resulted in 72% and 83% reduction in mf count on days 15 and 30, respectively, and the maximum reduction in mf count (91%) was achieved on day 75 post-treatment. However, treatment with tetracycline (10 mg/kg/day for 40 days) followed by acaciasides (10 mg/kg/day for 7 days) resulted in almost 100% clearance of mf at a faster rate on day 45 post-treatment and ensured long-term (until 4 months post-treatment) protection against microfilaremia. Data from polymerase chain reaction analysis reveals that compared to untreated dogs, in treated dogs, there was marked reduction in Wolbachia specific wsp markers in fast depleting mf population. The present data indicate that prior tetracycline treatment enhances microfilaricidal activity of saponins. This effect may be additive or synergistic as the worms are weakened by Wolbachia depletion, and these weakened microfilariae are possibly killed by the saponins.

Antimicrobial activity of saponins from Acacia auriculiformis.

Acaciaside A and B, two acylated bisglycoside saponins originally isolated from the funicles of Acacia auriculiformis, are known to have antihelminthic activity. Their antifungal and antibacterial activities were investigated. Complete inhibition of conidial germination of Aspergillus ochraceous and Curvularia lunata was recorded at 300 microg/ml or less whereas to inhibit the growth of Bacillus megaterium, Salmonella typhimurium and Pseudomonas aeruginosa 700 microg/ml or higher concentrations of the mixture was required. Two catabolic enzymes, phosphofructokinase and isocitrate dehydrogenase, responded differentially in fungi and bacteria against sublethal concentrations of the compound when assayed from their cell free extracts. An increased specific activity of the enzymes in bacteria and a decrease activity in fungi indicate a possible different mechanism of inhibition of saponins on the organisms tested.

Enhancement of membrane damage by saponins isolated from Acacia auriculiformis.

Acaciaside A and B, two acylated triterpenoid bisglycosides isolated from the funicles of Acacia auriculiformis, are known to have antihelmintic activity. Since the saponins contain a conjugated unsaturated system that is highly susceptible to peroxidation, we investigated the interaction of saponins and membrane using rat liver microsomes as our model. Microsomal membranes were incubated with saponins at 30 degrees C for 2 hr. Following incubation, lipid peroxidation was measured in terms of malondialdehyde and conjugated diene. Our results showed that incubation of microsomal membranes with saponins increased both malondialdehyde and conjugated diene. The results suggest that in our model, saponins enhance the membrane lipid peroxidation.

Cestocidal activity of Acacia auriculiformis.

The cestocidal activity of Acacia auriculiformis was evaluated using rats each harbouring a single adult worm of Hymenolepis diminuta. The ethanol extract (300 mg/kg/day) and the saponins (200 mg/kg/day) obtained from the funicles of A. auriculiformis, were administered orally to two groups each of 10 rats, respectively, on day 20 after oral inoculation with a single cysticercoid of H. diminuta. Adult worms were expelled within 5 days from rats treated with the ethanol extract and within 3 days from those treated with saponins. No appreciable side effects were observed in the treated rats.