Hepatotoxicity potential of saw palmetto (Serenoa repens) in rats.

Saw palmetto (Serenoa repens L.) is an herbal drug used to treat symptoms of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). There has been a report that a preparation containing this herb has caused cholestatic hepatitis in one person and some indications exist that it may have the potential to produce liver toxicity. The purpose of this study was to evaluate the effect of saw palmetto on rat liver function by measuring its effects on several enzymes and formation of malondialdehyde (MDA), a byproduct of lipid peroxidation. A significant increase in these parameters is considered an indication of liver toxicity. Thirty-six rats were divided into 6 groups of 6 animals each. They were treated for 2 or 4 weeks with a placebo or saw palmetto at doses of 9.14 or 22.86 mg/kg/body wt./day; that is, 2 x and 5 x the maximum recommended daily human dosages. After 2 or 4 weeks, the animals were sacrificed and blood was collected to prepare serum for enzyme assays, which were performed using commercially available kits. A portion of the liver was removed, and a homogenate prepared for the lipid peroxidation assay. Results showed no significant difference in animal body weight, enzyme activity, or MDA formation at either time or dosage level, as compared to controls. The data indicate that at the doses and time periods tested, saw palmetto did not produce any significant effect on the normal biological markers of liver toxicity.

Isolation and characterization of myogenic satellite cells from the muscular dystrophic hamster.

Myogenic satellite cells were isolated from control and dystrophic hamster diaphragms to examine cellular mechanisms involved in the physiology of muscular dystrophy. The Bio 14.6 dystrophic hamster, which possesses a defect in the delta-sarcoglycan gene, develops biochemical and physical symptoms of Duchenne-like and limb girdle muscular dystrophies. Because primary cultures of the control and dystrophic satellite cells became extensively contaminated with non-myogenic cells during proliferation, cell clones were developed to provide pure cultures for study. Cell culture conditions were optimized with the use of Ham's F-12K medium containing 10% fetal bovine serum +5% horse serum + 10 ng/mL basic fibroblast growth factor + 50 microg/mL porcine gelatin. Proliferation rates of the two clonal cultures were similar between the two lines. Satellite cell-derived myotubes from both primary cultures and clones differed between control and dystrophic animals. Dystrophic myotubes tended to be long and narrow, while the control-derived myotubes were broader. Measurement of muscle-specific creatine kinase during differentiation revealed that the dystrophic myotubes possessed higher creatine kinase levels than control myotubes (up to 146-fold at 168 h). The results demonstrate that satellite cells can be isolated from the hamster and may provide a useful tool to study muscular dystrophies associated with defects in the sarcoglycan complex and the involvement of sarcoglycans in normal skeletal muscle growth and development.

Effects of thyroxine and naloxone administration on metabolism and ventilation in hamsters.

This study examined the interaction between hyperthyroidism and opioid receptor function on control of ventilation and metabolism in male Harlan hamsters 4 and 8 weeks after implanting thyroxine (T(4)) or placebo pellets. Metabolism, but not body temperature, increased in T(4)-treated hamsters relative to placebo-treated animals. After 4 weeks, body weights were greater in the T(4)-treated hamsters, but comparable to controls after 8 weeks. At that time, body length was greater in T(4)-treated hamsters than in controls. Thyroxine did not affect ventilation in air or in response to CO(2). Naloxone, an opioid receptor antagonist, decreased metabolism in T(4)-treated, but not in placebo-treated hamsters without affecting ventilation in air in either group. In the placebo group naloxone augmented the ventilatory response to hypercapnia by increasing frequency. These results negate our hypotheses that: (1) hyperthyroid hamsters exhibit greater ventilation in air and in response to hypercapnia than controls; and (2) that naloxone augments these effects.

Study of in vitro and in vitro effects of isradipine in skeletal muscles and interaction with some drugs.

The effects of the calcium channel blocker isradipine were studied in the indirectly and directly stimulated mouse diaphragm and in the anesthetized rat to determine its potency, reversibility and interaction with a number of drugs. Initially, it potentiated both indirect and direct twitches followed by a reduction. With tetanic contractions, no potentiation was obtained, only a reduction, which was complete or near complete at the highest concentration tested (10(-4) M). In combination, isradipine reduced the IC50 and IC90 values for the antibiotics gentamicin, polymyxin B and clindamycin, d-rubocurarine and magnesium ions. Depression of contraction caused by isradipine or in combination could be reversed to varying degrees by washout, elevated calcium ions, neostigmine or 4-aminopyridine. Spontaneous recovery from the effects of isradipine alone or in combination was slow and usually incomplete. For in vivo experiments, severe cardiovascular depressant effects of isradipine limited its exposure to lower concentrations and for shorter periods. Under these conditions, it had no effect on heart rate. However, both systolic and diastolic blood pressure were significantly reduced, while pulse pressure was increased. After an initial potentiation muscle contraction was maximally reduced to 55% of control. This study indicates that acute administration of isradipine may aggravate neuromuscular effects of antibiotics, muscle relaxants or hypermagnesemia, although it is unlikely that spontaneous recovery or reversibility of muscular activity by suitable reversal agents will be affected. However, prolonged use of the drug may be more difficult to reverse.

Professionals' perceptions of psychotropic medication in residential facilities for individuals with mental retardation.

Professional staff in four state facilities for individuals with mental retardation were surveyed to determine their perceptions, knowledge and opinions regarding the use of psychotropic medication. A large majority of the 377 respondents indicated that the physicians in their facilities were primarily responsible for medication-related decisions. Under ideal conditions, however, all professional staff and parents were seen as having a greater influence in the decision-making process. Aggression, delusions and hallucinations, self-injury, other psychiatric disorders, and anxiety were rated as disorders most likely to result in medication therapy. Behaviour modification was viewed as a suitable alternative to drug treatment for acting out and aggression. The professionals indicated that behavioural observation was the most influential assessment technique in current usage, followed by global impressions and informal diaries. Over 80% of the respondents perceived their preservice and inservice training on issues related to the use of psychotropic medication to treat behaviour problems as inadequate, with 96% of them desiring continuing education. These findings were compared to data from similar studies of populations with other disabilities, and suggestions for modifications in the current decision-making processes related to the use of psychotropic medication in institutionalized individuals with mental retardation are discussed.

Common variable immunodeficiency (CVID) in northern India.

Fourteen patients with common variable immunodeficiency (CVID) were studied. The common clinical manifestations were recurrent sore throat, sinusitis, respiratory infections, diarrhea, and malnutrition. All had low IgG, with normal cell-mediated immunity. Treatment with immunoglobulin and/or plasma was effective in most of them. There were no severe adverse events with the therapy.

Methotrexate in psoriatic arthritis.

Thirty three patients with psoriatic arthritis were treated with starting dose of 7.5 mg of methotrexate orally, every week for a period of 6 months to 7 years (mean 2.2 years) along with non-steroidal anti-inflammatory agents. The dose of methotrexate during the course of therapy ranged 5 to 15 mg/week (mean 7.8 mg). There was complete to partial remission in arthritis and psoriatic skin lesions in 94% (31) patients. No response was noticed in 2 patients. Regular monitoring of haematological, renal and liver function tests was done. No significant side effects of the drug, requiring discontinuation of the therapy, were seen during the treatment. Methotrexate can be used early in the course of psoriatic arthritis with good results.

Effects of TMB-8, a putative calcium antagonist, on neuromuscular transmission and muscle contractility in the mouse phrenic nerve-hemidiaphragm preparation.

The effects of TMB-8 [8-(N.N.-diethylamino)octyl-3,4,5-trimethoxybenzoate], a putative calcium antagonist, on directly and indirectly evoked isometric twitches, tetanic contractions and potassium- and caffeine-induced contractures, were investigated in the mouse isolated phrenic nerve-hemidiaphragm preparation. In the lowest concentration tested (10(-6) M), TMB-8 produced an augmentation of both directly and indirectly induced twitches. In higher concentrations (10(-5)-3 x 10(-5) M), this augmentation was followed by twitch reduction. In the highest concentrations (10(-4) M-3 x 10(-4) M), only twitch reduction in a concentration-dependent manner was observed. TMB-8 also depressed both directly and indirectly induced tetanic contractions. However, the drug was more effective in depressing neurotransmission than in reducing muscle contractility. Elevated Ca2+ (4-8 mM) or 3,4-diaminopyridine (10(-4) M) produced a good reversal of neuromuscular blockade but this effect was transient. Pretreatment with 4 mM Ca2+ had no significant effect on the time required to produce a 50% or a 90% inhibition of directly or indirectly induced twitches. However, 8 mM Ca2+ significantly prolonged the inhibitory effects of TMB-8 on indirectly, but not directly induced twitches. On the other hand, neostigmine (3 microM) appeared to hasten the blockade of transmission. Submaximal potassium-induced contractures were markedly depressed while caffeine-induced contractures were only slightly depressed by TMB-8 in the concentration range tested (10(-5)-3 x 10(-4) M). The results are consistent with the hypothesis that TMB-8 inhibits skeletal muscle contractility by a reduction in transmembrane Ca2+ movement, a depression of postsynaptic acetylcholine receptor sensitivity, and a decreased mobilization of sequestered calcium from the sarcoplasmic reticulum.

Long distance truck drivers in India: HIV infection and their possible role in disseminating HIV into rural areas.

In this study, a large number of truck drivers were found to be having sex with the prostitutes in rural areas along the highways of India. Some were having sex with men also. HIV/AIDS awareness and condom use was poor among them. Three out of 302 truck drivers were found to be infected with HIV. The truck drivers could play an important role in the spread of the infection in rural India.

PIP: Data on HIV risk behavior, condom use, and HIV/AIDS awareness were obtained through a survey and interviews with 200 randomly selected truck drivers, 21 highway prostitutes, and 27 male prostitutes in Delhi and nearby areas during October 1990-December 1990. 302 randomly selected truck drivers were tested for HIV infection; none of the highway prostitutes consented to the HIV antibody test. A survey was again conducted among 100 randomly selected truck drivers in November 1991 and November 1992 to assess the levels of current HIV awareness and risk behavior. The drivers were aged 20-40 years, wayside prostitutes aged 32-40 years, and part-time male prostitutes aged 16-34 years. 60% of the drivers were married with families, as were all of the wayside prostitutes, and none of the male prostitutes. 78% of drivers admitted having multiple heterosexual partners, including prostitutes, and 5% admitted to regular homosexual sexual encounters. Only 20% of the drivers in 1990, however, had heard about HIV/AIDS. 25% of this subgroup was aware that HIV may be transmitted sexually, 28% of promiscuous drivers used condoms regularly, none admitted taking IV drugs, 35% reported histories of either urethral discharge or genital ulcers, and 3 of the 302 men tested were found to be infected with HIV. None of the 21 highway prostitutes had heard about AIDS, although 21 of the 27 male prostitutes had. All highway prostitutes admitted having at least one episode of unprotected sex with their sex partners in the previous fortnight, while all of the male sex workers would allow unprotected sex if their partners desired. Some male prostitutes were also paid blood donors. None of the prostitutes consented to having an HIV antibody test. The authors note that while HIV awareness improved in subsequent years, the practice of safe sex did not. 42% and 56% of the drivers had heard about HIV/AIDS in 1991 and 1992, respectively, but 77% and 68% were nonetheless engaging in occasional unprotected sex. Truck drivers engaging in unprotected sexual intercourse with multiple partners in rural India could be major vectors of HIV infection.

Clinical effects of buspirone on intractable self-injury in adults with mental retardation.

OBJECTIVE: The efficacy of buspirone in controlling self-injurious behavior was examined in five individuals with mental retardation. Buspirone was used alone in two individuals and as an adjunct to thioridazine in the other three. METHOD: Standard behavioral observation methods were used to collect data on the number of self-injurious responses of the individuals during baseline and several doses of buspirone in an open trial. RESULTS: When compared with baseline levels, all five individuals showed some response to buspirone, with reductions in self-injury ranging from 13% to 72%, depending on the dose. The most effective dose of buspirone was 30 mg/day for three individuals and 52.5 mg/day for the other two. These individuals were maintained for 6 to 33 weeks on their most effective dose. Coexistent symptoms of anxiety did not predict a favorable response to buspirone therapy. CONCLUSIONS: Buspirone showed a mixed but generally favorable response in controlling intractable self-injury in this and four previous studies reporting similar cases. However, the drug should not be endorsed as a proved treatment for self-injury until similar results have been obtained from well-controlled studies of its efficacy.

Experience of HIV prevention interventions among female sex workers in Delhi, India.

This paper describes the effect of HIV prevention intervention among female sex workers in Delhi. Over a 2-year period we found a marked increase in condom use with little increase in HIV seroprevalence. The prevalence of HIV infection did not increase during the study period (1 positive among 701 in 1988 vs 1 positive in 600 in 1990).

PIP: HIV infection in India is firmly entrenched mainly among promiscuous heterosexuals and recipients of blood and blood products. Many female prostitutes are infected, with the prevalence of infection rapidly increasing within the subpopulation. Various interventions were therefore launched in different places in India to prevent the further spread of HIV. This study describes the effect of an HIV prevention intervention among female prostitutes in Delhi. An intense HIV awareness campaign was held among female prostitutes in Delhi during April-May 1988 involving group discussion, poster and pamphlet distribution, a short video film, peer counselling, and the counselling of madams, pimps, prostitutes, and young men who pose as prostitutes' husbands to provide emotional and physical security. At baseline, one woman among 701 serotested was identified HIV-seropositive. 5% were aware of HIV/AIDS and 20% used condoms regularly. In 1990, again, only one among 600 serotested was seropositive for HIV. 70%, however, were aware of HIV/AIDS and 50% used condoms regularly; 40% used condoms most of the time.

Fluoxetine treatment of severe self-injury in young adults with mental retardation.

Dysfunction of the serotonergic system has been implicated in the development and maintenance of self-injury in some persons with mental retardation. Several preliminary reports have suggested that fluoxetine, a drug that blocks the reuptake of serotonin, may decrease self-injury in these individuals. Of the 44 cases of self-injury treated with fluoxetine and previously reported in the literature, 42 demonstrated a beneficial response to the drug. We report four additional cases of adults with mental retardation whose self-injury was treated with fluoxetine. Each of these individuals benefited from fluoxetine to some extent, with average decreases in self-injury ranging from 20% to 88% when compared with baseline levels. These findings, combined with those from previously published case studies, emphasize the need for well-controlled studies to more adequately assess the effects of fluoxetine on self-injury.

Studies on the muscle-paralyzing components of the juice of the banana plant.

The stem juice of the banana plant (Musa species) has been used as an arrow poison by African tribesmen. Lyophilized, partially purified extracts of the juice augment and then block both directly and indirectly evoked contractions of the mouse diaphragm. We have isolated, purified and determined the chemical composition of the active ingredients, and characterized their pharmacological activity. The lyophilized sample was extracted with a methanol-water (MeOH-H2O) (50/50) mixture and vacuum filtered. The filtrate was rotary evaporated and crystallized in a MeOH-H2O mixture to yield potassium nitrate crystals (melting point 332-334 degrees C). The filtrate was concentrated and chromatographed over Sephadex LH-20 gel using MeOH-H2O (40/60) as the eluent. The active component was found to be magnesium nitrate crystals (melting point 87-89 degrees C). In the mouse isolated phrenic nerve-hemidiaphragm preparation, the pharmacological profile of the first component was similar to that for authentic potassium nitrate which augments in low concentrations, and in higher concentrations augments, and then blocks both directly evoked muscle contraction the neuromuscular transmission. The second component had a profile of activity similar to that for authentic magnesium nitrate which only blocks neuromuscular transmission. It can be concluded that the two major active principles in the banana stem juice are potassium nitrate and magnesium nitrate.

Prevalence of systemic lupus erythematosus in India.

Prevalence of systemic lupus erythematosus (SLE) was studied in the northern Indian population by means of a two-pronged approach: (a) antinuclear antibody (ANA) screening of the general population by a new well-standardized finger-prick 'filter paper' technique (sensitivity and specificity: 95.4% and 86.2%, respectively); and (b) a questionnaire survey carried out primarily by trained personnel in the community (sensitivity and specificity: 100% and 68.6% respectively). The low specificity of the two methods was improved by the introduction of a step of secondary screening by the authors, thus excluding false positives. ANA screening of 52,062 individuals yielded 13 positive results, of which only two were found to be true cases of SLE after secondary screening. Questionnaire survey of 39,826 individuals similarly yielded 3393 positive results. On secondary screening, only one of these persons was found to be a case of SLE. Thus, three cases of SLE were detected in a population survey of 91,888, giving a point prevalence of 3.2 per 100,000 (95% CI = 0-6.86 per 100,000). The reported prevalence of SLE ranges from 14 to 60 per 100,000. Thus, the prevalence of SLE in India is comparatively low. Although the reasons for low prevalence are not clear, the study used highly sensitive methodology and it is therefore unlikely that SLE cases were missed. It is hypothesized that SLE is a disease of modernization and therefore its prevalence in a predominantly rural population like that of India is low.

Pneumocystis carinii infection in patients of AIDS in India.

This is the first report of Pneumocystis carinii infection seen in patients with AIDS in India. Two of the three patients were of Indian origin while the third was an American tourist. This report indicates that the technical problem of demonstrating P carinii may be an important factor underlying the diagnosis of PCP.

Inosithin neutralization test to measure lupus anticoagulants.

The inosithin neutralization test was performed in 14 patients in whom lupus anticoagulant was detected. To test its specificity, it was also performed in 10 patients with severe hemophilia and in three patients with Factor VIII inhibitors. Prolonged kaolin clotting time was corrected by adding varying amounts of inosithin (Asolectin, 0.19 to 100 micrograms), a soybean-derived phospholipid, in all patients with lupus anticoagulant but not in patients with hemophilia or in two patients with Factor VIII inhibitors. In one patient, both Factor VIII inhibitors and lupus anticoagulant were present. The concentration of lupus anticoagulant in a patient was expressed as the amount of inosithin (measured in micrograms) required to normalize the prolonged kaolin clotting time. This amount correlated significantly with the occurrence of thrombosis and/or recurrent abortion. The inosithin neutralization test is useful to measure lupus anticoagulant.