Sub-clinical infection with Mycobacterium leprae in household contacts of leprosy

870 household contacts of leprosy patients were examined for sub-clinical infection with M. leprae by smear (skin and nasal), lepromin and FLA-ABS tests. 0.6%, 3.3%, 71.5% and 14.4% of the contacts were found to be positive for skin smear, nasal smear, lepromin and FLA-ABS tests respectively. An analysis of the results revealed that 4% of the lepromin positive contacts and 3.6% of the lepromin negative contacts were positive to both FLA-ABS and skin or nasal smear.     

p66Shc—a longevity redox protein in human prostate cancer progression and metastasis

p66Shc, a 66 kDa proto-oncogene Src homologous-collagen homologue (Shc) adaptor protein, is classically known in mediating receptor tyrosine kinase signaling and recently identified as a sensor to oxidative stress-induced apoptosis and as a longevity protein in mammals. The expression of p66Shc is decreased in mice and increased in human fibroblasts upon aging and in aging-related diseases, including prostate cancer. p66Shc protein level correlates with the proliferation of several carcinoma cells and can be regulated by steroid hormones. Recent advances point that p66Shc protein plays a role in mediating cross-talk between steroid hormones and redox signals by serving as a common convergence point in signaling pathways on cell proliferation and apoptosis. This article first reviews the unique function of p66Shc protein in regulating oxidative stress-induced apoptosis. Subsequently, we discuss its novel role in androgen-regulated prostate cancer cell proliferation and metastasis and the mechanism by which it mediates androgen action via the redox signaling pathway. The data together indicate that p66Shc might be a useful biomarker for the prognosis of prostate cancer and serve as an effective target for its cancer treatment.     

Impact of ivermectin drug combinations on Pediculus humanus capitis infestation in primary schoolchildren of south Indian rural villages

Background  Antifilarial drug combinations including ivermectin provide antifilarial activity with ancillary benefits on intestinal helminths and ectoparasites, such as chiggers and lice. The impact of single oral dose of antifilarial drugs, viz; (1) diethylcarbamazine (DEC) alone, (ii) DEC + albendazole (ALB), (iii) ivermectin (IVR) + DEC and (iv) IVR + ALB, was determined, on the head louse ( Pediculus humanus capitis ) in primary school children in a rural community in south India.
Methods  Primary school children ( n  = 534) of age 6–10 years from four villages of South India were examined for the presence of head lice before and after single dose of DEC + ivermectin drug combination. The effectiveness and the duration of cure sustained by these drugs were quantified. The head louse was examined by "combing method" during post-treatment periods at 15, 45, 60 and 75 days interval.
Results  The antifilarial drug consumption rate was similar (96–98%) in all treatment arms. In pre-treatment survey the prevalence of head lice in children administered with DEC, DEC + ALB, IVR + DEC and IVR + ALB arm was 86%, 80%, 87% and 80%, respectively, with the latter two arms demonstrating significant reduction in louse infestation ( P  < 0.05) for 60 days.
Conclusion  Single dose with IVR combination demonstrates a greater impact in reducing head louse infestation in the endemic rural communities for nearly 60 days. Therefore, in regions such as Africa where ivermectin is part of the antifilariasis campaign, this drug will have an additional benefit in reducing head lice infestation.     

High-dose 166Ho-DOTMP in myeloablative treatment of multiple myeloma: pharmacokinetics, biodistribution, and absorbed dose estimation.

Thirty-two patients with multiple myeloma were treated with high doses of 166Ho-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonic acid (DOTMP) and were a subset of patients enrolled in a multicenter phase I/II dose escalation myeloablative trial. 166Ho with beta-emission (half-life, 26.8 h; beta-particle energies, 1.85 MeV [51%] and 1.77 MeV [48%]; gamma-photons, 80.6 keV [6.6%] and 1.38 MeV [0.9%]) was complexed to DOTMP, a macrocyclic tetraphosphonate. Pharmacokinetics, dosimetry, and biodistribution were studied. METHODS: Patients were treated at escalating dose levels of 20, 30, and 40 Gy to the bone marrow in combination with high-dose melphalan, with or without total-body irradiation, to evaluate toxicity and efficacy. After infusion with 1,110 MBq (30 mCi) of 166Ho-DOTMP for evaluation of biodistribution and dosimetry calculation, patients received the calculated amount of radioactivity for therapy in a single administration based on estimated dose calculations. RESULTS: Thirty-two patients participated in the study and were then treated. The average amount of administered radioactivity was 74.3 GBq (2,007 mCi) (range, 21.5-147.5 GBq [581-3,987 mCi]) of 166Ho-DOTMP. CONCLUSION: 166Ho-DOTMP has physical and pharmacokinetic characteristics compatible with high-dose myeloablative treatment of multiple myeloma.     

Bilateral massive pulmonary thromboembolism in a young patient treated with supportive measures and an inferior vena cava filter with excellent outcome

Acute pulmonary embolism (PE) is a common and often fatal disease with a mortality rate of more than 30% in untreated patients. There is a twofold increase in mortality in patients with massive PEs who do not receive treatment. Recurrent embolism is the most common cause of death. A 48-year-old woman presented to Tan Tock Seng Hospital, Singapore, on December 16, 2009, with a massive pulmonary thromboembolism. She was admitted to the intensive care unit and treated with supportive measures, ventilatory support, antibiotics and ionotropes. The patient was diagnosed with urosepsis with septicemic shock, disseminated intravascular coagulation, acute renal failure, high anion gap metabolic acidosis, iron-deficiency anemia secondary to menorrhagia, and a uterine mass with high cancer antigen 125, although malignancy was ruled out. Anticoagulation or thrombolysis could not be provided in view of coagulopathy. The patient subsequently underwent inferior vena cava filter insertion on December 31, 2009. The patient showed clinical improvement over the next two weeks with antibiotics and supportive measures. If there is a contraindication to anticoagulation or thrombolysis, massive pulmonary thromboembolism should be treated aggressively with supportive measures. Inferior vena cava filter insertion should be instituted early to prevent recurrent PE, which can be fatal. It may take weeks before the patient displays clinical improvement.     

Effects of the anti-malarial compound cryptolepine and its analogues in human lymphocytes and sperm in the Comet assay

Malaria is a mosquito-borne infectious disease caused by the genus Plasmodium. It causes one million deaths per year in African children under the age of 5 years. There is an increasing development of resistance of malarial parasites to chloroquine and other currently used anti-malarial drugs. Some plant products such as the indoloquinoline alkaloid cryptolepine have been shown to have potent activity against P. falciparum in vitro. On account of its toxicity, cryptolepine is not suitable for use as an antimalarial drug but a number of analogues of cryptolepine have been synthesised in an attempt to find compounds that have reduced cytotoxicity and these have been investigated in the present study in human sperm and lymphocytes using the Comet assay. The results suggest that cryptolepine and the analogues cause DNA damage in lymphocytes, but appear to have no effect on human sperm at the assessed doses. In the context of antimalarial drug development, the data suggest that all cryptolepine compounds and in particular 2,7-dibromocryptolepine cause DNA damage and therefore may not be suitable for pre clinical development as antimalarial agents.     

Radiosensitizing effect of ferulic acid on human cervical carcinoma cells in vitro

Radiotherapy may be effectively combined with plant derived radiosensitizers. Ferulic acid, a naturally occurring phenolic acid, has been reported to have free radical producing properties. In the present study, the radiosensitisation potential of ferulic acid has been tested in two cervical cancer cell lines (HeLa and ME-180) in vitro. Percentage of growth inhibition (MTT assay), colony survival, levels of lipid peroxidation (TBARS, CD and LHP), antioxidant status (SOD, CAT, GPx and GSH), oxidative DNA damage (% tail DNA, tail length, tail moment and Olive tail moment), apoptotic morphological changes (AO/EtBr staining) and intracellular ROS levels (DCFH-DA) were estimated. The present results show that ferulic acid (FA) enhances radiation effects by increasing lipid peroxidative markers in HeLa and ME-180 cells. We observed significant enhancement of ROS levels during ferulic acid plus radiation treatment. FA treatment alone increased intracellular ROS levels indicate its prooxidant nature. Similarly, we observed enhanced oxidative DNA damage and apoptotic morphological changes in FA plus radiation treated cells. The present data suggest radiation sensitizing property of FA in cervical cancer cells. Further investigations warrants to substantiate the present findings.     

Prevalence of intestinal parasitic infestation in HIV/AIDS patients with diarrhea in Madurai City, South India

The prevalence and pattern of parasitic infestation among 80 HIV/AIDS patients with diarrhea in Madurai, south India, was studied by microscopy. Eighty HIV-negative patients were used as controls. Intestinal parasites were detected in 31 HIV/AIDS patients (38.7%) and in 14 (17.5%) HIV-negative patients, a difference that was statistically significant (P < 0.05). In HIV/AIDS patients with diarrhea, protozoa accounted for the majority of diarrhea cases (Entamoeba spp. 37.5%, Cryptosporidium parvum 28.7%). It is therefore suggested that enteric infections are more common in HIV-infected patients than in HIV-negative persons in south India, and this may be due to differences in immunological profile, susceptibility as well as factors related to sanitation and the environment.     

Diffusion tensor anisotropy in adolescents and adults

We acquired diffusion tensor images on 33 normal adults aged 22-64 and 15 adolescents aged 14-21. We assessed relative anisotropy in stereotaxically located regions of interest in the internal capsule, corpus callosum, anterior thalamic radiations, frontal anterior fasciculus, fronto-occipital fasciculus, temporal lobe white matter, cingulum bundle, frontal inferior longitudinal fasciculus, frontal superior longitudinal fasciculus, and optic radiations. All of these structures except the optic radiations, corpus callosum, and frontal inferior longitudinal fasciculus exhibited differences in anisotropy between adolescents and adults. Areas with anisotropy increasing with age included the anterior limb of the internal capsule, superior levels of the frontal superior longitudinal fasciculus and the inferior portion of the temporal white matter. Areas with anisotropy decreasing with age included the posterior limb of the internal capsule, anterior thalamic radiations, fronto-occipital fasciculus, anterior portion of the frontal anterior fasciculus, inferior portion of the frontal superior longitudinal fasciculus, cingulum bundle and superior portion of the temporal axis. Sex differences were found in the majority of areas but were most marked in the cingulum bundle and internal capsule. These results suggest continuing white matter development between adolescence and adulthood.