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Biomedical subjects

S Ananthakrishnan

Publications and source records attributed to S Ananthakrishnan.

18 recordsLinked to original sources

K+ channel types targeted by synthetic OSK1, a toxin from Orthochirus scrobiculosus scorpion venom.

OSK1 (alpha-KTx3.7) is a 38-residue toxin cross-linked by three disulphide bridges that was initially isolated from the venom of the Asian scorpion Orthochirus scrobiculosus. OSK1 and several structural analogues were produced by solid-phase chemical synthesis, and were tested for lethality in mice and for their efficacy in blocking a series of 14 voltage-gated and Ca2+-activated K+ channels in vitro. In the present paper, we report that OSK1 is lethal in mice by intracerebroventricular injection, with a LD50 (50% lethal dose) value of 2 microg/kg. OSK1 blocks K(v)1.1, K(v)1.2, K(v)1.3 channels potently and K(Ca)3.1 channel moderately, with IC50 values of 0.6, 5.4, 0.014 and 225 nM respectively. Structural analogues of OSK1, in which we mutated positions 16 (Glu16-->Lys) and/or 20 (Lys20-->Asp) to amino acid residues that are conserved in all other members of the alpha-KTx3 toxin family except OSK1, were also produced and tested. Among the OSK1 analogues, [K16,D20]-OSK1 (OSK1 with Glu16-->Lys and Lys20-->Asp mutations) shows an increased potency on K(v)1.3 channel, with an IC50 value of 0.003 nM, without loss of activity on K(Ca)3.1 channel. These data suggest that OSK1 or [K16,D20]-OSK1 could serve as leads for the design and production of new immunosuppressive drugs.

Amino Acid Sequence↗

Entry lesions in bancroftian filarial lymphoedema patients--a clinical observation.

The prevalence of entry lesions in limbs was significantly higher in limbs with filarial lymphoedema (80.88%) than in normal limbs (42.86%, P = 0.000012). Among the various entry lesions in the lymphoedematous limbs, the prevalence of web space intertrigo was significantly higher in those who had acute dermatolymphangioadenitis (ADLA) than those who did not have ADLA (P = 0.04). Entry lesions were present only in 25% of those not using footwear, while 84.3% of those using footwear regularly or irregularly had these lesions (P = 0.01). None of the patients with good limb hygiene had ADLA, while 64% of those with fair to poor limb hygiene had ADLA (P = 0.02). Since the majority of the entry lesions were asymptomatic, training of patients and health care givers to specifically look for and treat these along with advice for good limb hygiene practices should form an important component of foot care programme for optimum filarial morbidity management.

Elephantiasis, Filarial↗

Cardiac involvement and scorpion envenomation in children.

Cardiac complications of 32 children with scorpion envenomation, during a 1-year period from August 1990 to August 1991 were studied. Sixteen children (50 per cent) were diagnosed as having myocarditis; of these in four children the presentation was subclinical. ECG changes were seen in 63 per cent of children envenomed and was a sensitive indicator of myocarditis. Sixty-nine per cent of children with myocarditis had left ventricular dysfunction as shown by echocardiography. Though statistically not significant, there was a correlation between prolonged QTc and LV dysfunction, which needs to be studied further. In those children who came for follow-up, the left ventricular function reversed to normal.

Animals↗

Scorpion envenomation in children in southern India.

The clinical presentation of 32 children with scorpion envenomation was analysed. The most common presentation was cold, clammy extremities with normal blood pressure. Myocarditis was present in 16 children (50%) and encephalopathy in four (12.5%). Two children died. ECG was a sensitive indicator of myocarditis which was subclinical in four children. Left ventricular dysfunction was a transient phenomenon. Myocarditis and encephalopathy were the two lethal complications observed. Serum free fatty acid levels were elevated two to three-fold in all symptomatic patients. Blood glucose levels were only mildly elevated and serum amylase levels and electrolytes were normal in all the children. No specific antivenom was given. In the absence of specific antivenom, early and active supportive treatment reduces the morbidity and mortality due to scorpion envenomation.

Animals↗

Loose stools in the early neonatal period.

During a two-year period, the various factors associated with loose stools in the early neonatal period were studied among hospital born babies. Low birth weight babies had a lower incidence of non-infective loose stools when compared to neonates with a birth weight of more than 2500 g (p < 0.001). Newborns delivered by Cesarean section (p < 0.001) and those born to women with more than two children (p < 0.02) had a greater frequency of loose stools. Initiation of supplementary feeding and administration of antibiotics were important factors in causing loose stools. Bacterial etiology could be found only in 9.3% of newborns having loose stools. A later onset of loose stools was noted in those, whose stool culture grew bacterial organisms. Only nine newborns with loose stools required antibiotic therapy. Although loose stools were less common among low birth weight babies, they often required treatment with antimicrobials. None of them developed any complications. Since majority of them are non-bacterial and non-infective, great caution must be exercised before administering antibiotics to newborns with loose stools.

Anti-Bacterial Agents↗

Poliomyelitis: 20 years--the Pondicherry experience.

During a 20-year period, 12,830 cases of acute poliomyelitis in children (aged 1 month-12 years) were seen in a South Indian teaching hospital (Pondicherry). Almost three-quarters (72.4%) of children were below the age of 2 years. The median age at onset of poliomyelitis shifted from 19.5 months (in the period 1968-1977) to 11 months (in the years 1978-1987). After 1981, epidemic peaks were noted every third year. 66.3% of cases had not received even a single dose of oral polio vaccine and 14.7% cases were vaccine failures (in the years 1983-1987). Provocation of poliomyelitis occurred in 66% of children and usually followed intragluteal injections associated with treatment of non-specific fevers. The overall mortality was 2.13%, the major cause of death being respiratory failure (60%). Polio virus type 1 was the major isolate among selected cases studied during 1983-1987. The risk factors identified in our study are lack of immunization and administration of intramuscular injections during the pre-paralytic phase. Ensuring early administration of multiple doses of oral polio vaccine to infants and avoiding intramuscular injections in young febrile children are important measures for the control of poliomyelitis--a continuing problem in Southern India.

Age Factors↗

Integrated programme for control of geohelminths: a perspective.

Infestation by geohelminths is an important public health problem in developing countries like India. It is a major cause of morbidity in school-age children who have the highest burden of worm infestation. Some of the morbid conditions attributed to intestinal helminthiasis are malnutrition, growth retardation, anaemia, vitamin A deficiency and impaired intellectual performance. Chemotherapy targeted at school-age children has been recommended as a cost-effective and feasible control programme for the control of geohelminths. To optimize resources a geohelminth control programme can be integrated with other existing national health programmes. The availability of drugs such as diethyl carbamazine (DEC) and albendazole, which have anthelminthic and antifilarial properties, opens the possibility of integrating a geohelminth control programme with a filaria control programme. However, co-administration of DEC and albendazole raises several issues of frequency of administration, efficacy, compliance and cost-effectiveness. Thus, integrating a geohelminth control programme with the existing mid-day meal or anaemia prophylaxis programme would be a more appropriate and cost-effective strategy to control geohelminths, alleviate the morbidity caused by them and improve the overall health of the community.

Adolescent↗

Intestinal geohelminthiasis in the developing world.

Intestinal parasitic helminths such as roundworms (Ascaris lumbricoides), hookworms (Ancylostoma doudenale and Necator americanus) and whipworm (Trichuris trichiura) are common in the developing world. Strongyloides stercoralis, though not so common, also contributes to health problems. The prevalence of intestinal worm infestation in India varies from 5% to 76%, which is similar to that in other developing countries. These parasitic infestations are acquired by ingestion, inhalation or penetration of the skin by the infective forms. Ascaris causes many intestinal and respiratory symptoms and plays an important role in precipitating protein-energy malnutrition in undernourished children. Hookworms cause anaemia and hypoproteinaemia. In areas where hookworm infestation is endemic, 90% of pregnant mothers are anaemic. Trichuriasis as a causative agent of human disease has only recently gained attention. Heavy infestation with T. trichiura can result in severe colitis and significant blood loss. This in turn can lead to impaired cognitive functions which are reversible on treatment. Though not as widely prevalent as the other geohelminths in India, Strongyloides stercoralis infestation can be fatal in debilitated and immunosuppressed children. So far, the impact of these parasites on the health of children has been underestimated and concentrated efforts to minimize the worm load and its consequences have not been given due importance in our health policies. This article reviews the pathophysiology, clinical impact and control options of the most commonly prevalent geohelminths in the developing world.

Adult↗