Pseutarin C,a prothrombin activator from Pseudonaja textilis venom: its structural and functional similarity to mammalian coagulation factor Xa-Va complex

Several snake venoms contain procoagulant proteins that can activate prothrombin. We have purified pseutarin C, a prothrombin activator from the venom of the Australian brown snake (Pseudonaja textilis). It converts prothrombin to thrombin by cleaving both the peptide bonds Arg(274)-Thr(275) and Arg(323)-Ile(324), similar to mammalian factor Xa. It is a protein complex (approximately 250 Kd) consisting of an enzymatic and a non- enzymatic subunit. These subunits were separated by reverse phase HPLC and their interactions with bovine factor Xa and factor Va were studied. The enzymatic subunit of pseutarin C has an approximately 13 fold higher affinity for bovine factor Va (K(d) of 11.4 nM for pseutarin C enzymatic subunit--bovine factor Va interaction as compared to a K(d) of 147.4 nM for the bovine factor Xa-Va interaction). The non-enzymatic component, however, was unable to activate bovine factor Xa. N-terminal sequence analysis of the catalytic subunit of pseutarin C showed approximately 60% homology to mammalian factor Xa and approximately 78% homology to trocarin, a group D prothrombin activator from Tropidechis carinatus venom. Structural information for the non-enzymatic subunit of pseutarin C was obtained by amino terminal sequencing of several internal peptides. The sequence data obtained indicates that the non-enzymatic subunit of pseutarin C has similar domain architecture like the mammalian factor Va and the overall homology is approximately 55%. Thus pseutarin C is the first venom procoagulant protein that is structurally and functionally similar to mammalian factor Xa-Va complex.     

Prepulse inhibition of the startle response in risperidone-treated patients: comparison with typical antipsychotics

Individuals with schizophrenia are known to show deficits in prepulse inhibition (PPI) of the startle response. PPI refers to a response suppression in reaction to a strong startling stimulus, if preceded briefly by a weak non-startling stimulus and represents a well-established animal model to investigate information processing deficits in schizophrenia. This study examined PPI of the startle acoustic response in schizophrenic patients given typical antipsychotics or a second generation atypical antipsychotic, risperidone, using a naturalistic between-subjects design. Two groups of male schizophrenic patients: (i) stable on a range of typical antipsychotics (n = 20), and (ii) stable on risperidone (n = 10) were tested for PPI (prepulse-to-pulse intervals: 30, 60, and 120 ms, prepulses 15 dB above the background) of the acoustic startle response, and compared with a group of healthy male subjects (n = 20). Patients on typical antipsychotics showed significantly less PPI with 30 and 60 ms prepulse trials than healthy subjects. Risperidone-treated patients did not differ from healthy subjects for PPI with any prepulse trials. Further longitudinal within-subject studies are now required to examine whether risperidone is superior to typical antipsychotics in improving information processing functions, as assessed by PPI of the acoustic startle response, in treatment-responsive male patients with schizophrenia.     

Clinical and molecular features of adPEO due to mutations in the Twinkle gene

We have analyzed Twinkle, the causative gene for autosomal dominant progressive external ophthalmoplegia (adPEO) on chromosome 10, in 11 Australian autosomal dominant progressive external ophthalmoplegia families of Caucasian origin, and investigated whether there are distinct molecular and clinical features associated with mutations in this gene. We found two new mutations in Twinkle, in 3 of the 11 pedigrees examined. One resides in the linker region of this gene while the other is in the primase domain. Both regions are highly conserved between species. Multiple deletions in the mtDNA from muscle are not always prominent and there are significant variations in the clinical presentation within and between families with mutations in the Twinkle gene. Therefore, genotype/phenotype predictions are difficult. No mutations were found in adenine nucleotide translocator 1 (ANT1), another known adPEO causative gene, in four of the seven remaining families investigated. Thus, Twinkle appears to be the most common gene associated with adPEO in Australian families.     

Med estimation for narrow band UV-B on type IV and type V skin in India

With an aim to determine minimum erythema dose of narrow band UV-B, 30 subjects, 20 with type IV skin and 10 with type V skin were subjected to graded incremental doses of 311-Narrow band UV-B phototherapy cabiner by Daavlin. Barely perceptible erythema 24 hours after exposure was taken as MED. 33.3% developed erythema at 745 mj, 26.6% at 620 mj, 23.3% at 1075 mj, and 10% at 1290 mj. The average MED for narrow band UV-B exposure for type 1V skin was 600 mj, [range 5515-755 mj] and for type V skin 1100 mj {range 895-1290 mj}. Better therapeutic response can be obtained by giving approximately 360-450 mj as initial irradiation dose for type 1 V skin and 600-825 mj for type V skin.     

A study on the comparison between clinical and microbiological diagnoses of sexually transmitted diseases

The efficacy of microbiological diagnosis in sexually transmitted diseases (STDs) has been evaluated in comparison with the clinical diagnosis. Amongst the clinical diagnoses of single STDs, syphilis, genital warts, gonorrhoea and herpes genitalis were the predominant ones. Syphilis was the most predominant infection in both the single and mixed STD infections in Chennai. Clinical diagnoses of trichomoniasis, genital chlamydiasis and genital herpes were more accurate and correlated well with laboratory investigations. On the other hand, clinical diagnoses of gonorrhoea, candidiasis and syphilis were less accurate. More over many of these cases, clinically diagnosed as single, infection, were also positive for other STDs in the laboratory investigations. Double infections were clinically diagnosed only in 7 cases as against 11 cases in microbiological tests and one triple infection diagnosed in microbiological tests was diagnosed only as single disease clinically. Therefore, the laboratory/microbiological investigations have been emphasised to have better accuracy of diagnosis of STDs.     

Cancer risk behaviors and screening rates among homeless adults in Los Angeles County.

The homeless encounter many barriers to health care and preventive services, while having an increased prevalence of most risk factors for cancer. A group of homeless adults (221) at nine different locations within Los Angeles County were surveyed during the summers of 1998 and 1999. A portion (71%) reported that they had had at least one rectal exam, 42% had a fecal occult blood test, 24% had a skin exam, and 23% had an endoscopy (flexible sigmoidoscopy or colonoscopy), and of the men aged 50+, only 19% had a prostate-specific antigen test in their lifetime. For women aged 40+, 55% had received a Pap smear, and 53% had a breast exam, but only 32% had a mammogram within the prior year. Among the sampled homeless population, 77% believed in the benefits of cancer screening, 79% were not fatalistic about cancer, 63% believed that early detection was efficacious, and 83% did not think it would be difficult to get screened. The majority of this population demonstrated accurate knowledge of cancer screening guidelines with the exception of endoscopy. Cancer screening rates of those surveyed were lower than the rates in California for endoscopy, prostate-specific antigen, mammography, and Pap smears. Given the lower cancer screening rates compounded by higher cancer risk factors, homeless populations need increased access to cancer screening tests, as well as education on the availability of free services. Additionally, facilities for the homeless and their staff should reinforce the purposes of cancer screening, provide more screening services, and implement institutional efforts, such as providing nutritious meals and sun protection products, to reduce high-risk behaviors and increase further access to cancer screening tests.     

Rapid assessment and response to injecting drug use in Madras, south India

HIV infection among injecting drug users (IDUs) is preventable, and in order to develop appropriate interventions, an assessment was carried out at Madras, South India using the Rapid Assessment and Response Guide on Injecting Drug Use developed by WHO. Data were collected with multiple methods from multiple sources using the principles of triangulation and induction. A total of 100 IDUs were interviewed. These interviews were complemented by focus groups and observations. A community advisory board ensured community ownership and participation. Findings showed that heroin, buprenorphine, diazepam and avil were the drugs most commonly injected. The use of pharmaceutical preparations as a 'cocktail' was also prevalent. Drug injectors interviewed were males, and most (81%) were from low-income groups living in slums. Direct (69%) as well as indirect sharing (94%) was common. Such unhygienic injecting practices, and the lack of access to sterile water, contribute to the high incidence of adverse health consequences. Compared with the buprenorphine injectors, heroin injectors were more likely to share injecting equipment (P=0.0022), inject more frequently (P=0.0013), have more drug using network members (P=0.0104), frequent 'shooting' locations (P=0.002), use the dealer's place to inject (P=0.0317), and face threats of arrest (P=0.0023). Many buprenorphine injectors managed their life without serious crises, and seemed to adopt a 'natural' harm reduction response. Sexual risk behaviour was prevalent among opioid users, and a history of commercial sex was associated with daily alcohol use (P=0.0221). The assessment led to an action plan which was presented and endorsed in an advocacy meeting by key stake-holders and decision-makers. The critical importance of implementing quality, accessible, community-oriented, and effective HIV interventions with the capacity to reach the majority of IDUs is discussed. Public health responses to injecting drug use must target changes among individuals at-risk, as well as in the community and risk environment.