Antiproliferative activity and electrochemical oxygen evolution by Ni(II) complexes of N'-(aroyl)-hydrazine carbodithioates.

The electrochemical water splitting by transition metal complexes is emerging very rapidly. The nickel complexes also play a very vital role in various biological activities. Here, three new ligands {H2mbhce = N'-(4-methyl-benzoyl), H2pchce = N'-(pyridine-carbonyl) and H2hbhce = N'-(2-hydroxy-benzoyl) hydrazine carbodithioic acid ethyl ester} and their corresponding Ni(II) complexes [Ni(Hmbhce)2(py)2] (1), [Ni(pchce)(o-phen)2]·CH3OH·H2O (2) and [Ni(hbhce)(o-phen)2]·1.75CHCl3·H2O (3) have been synthesized and fully characterized by various physicochemical and X-ray crystallography techniques. The photoluminescence study and thermal degradations were also examined. The treatment of K562 cells with the increasing concentrations of the nickel salts, ligands, and complexes 1, 2, and 3 showed dose-dependent cytotoxicity. The cytotoxic activity of ligands reveals that ligand H2mbhce is more potent in inhibiting the growth of tumor cells in comparison to other ligands H2pbhce and H2hbhce. Cytotoxicity assay results indicate that all complexes have remarkable cytotoxic potential in comparison to either nickel salts or the free ligands. Among these complexes, complex 1 has significantly better anti-tumor activity as compared to complexes 2 and 3. The electrochemical study of complexes 1, 2, and 3 for water oxidation reveals that all the complexes possess admirable electrocatalytic activity towards oxygen evolution reaction (OER) and have lower overpotential (328, 338, and 370 mV, respectively) than many previously reported complexes and RuO2 (390 mV). Among complexes 1, 2, and 3, complex-2 shows a better water oxidation response. Consequently, these complexes have great potential to be utilized in fuel cells. The more reliable electrochemical parameter TOF is also calculated for all three complexes.

Hepatic pathology in AIDS: a pathological study from Mumbai, India.

OBJECTIVES: To assess the spectrum of hepatic disorders in AIDS, liver specimens from 171 patients (155 autopsies and 16 biopsies) were reviewed. METHODS: A retrospective and prospective study of 171 autopsy and biopsy specimens was carried out at a tertiary level hospital in Mumbai, India. RESULTS: Of the patients included in the study, 127 (74%) were male and 44 (26%) were female. The heterosexual route was the predominant mode of HIV transmission, identified in 163 (95%) patients. A total of 99 of 171 patients (58%) showed significant pathological lesions, and the most common pathological processes involving the liver appeared to be secondary to infections. None of our patients showed isolated infectious diseases of the liver. The spectrum of liver diseases identified was as follows: tuberculosis in 70 patients (41%), cryptococcosis in eight (5%), cytomegalovirus infection in six (3%), hepatitis B infection in five (3%), candidiasis in one (0.5%), malaria in one (0.5%), cirrhosis in six (3%), amyloidosis in one (0.5%) and primary hepatic lymphoma in one (0.5%). CONCLUSIONS: AIDS patients were found to have a high prevalence of underlying hepatic abnormalities. The spectrum of disease among patients with AIDS in India differs from that in developed countries. Our results suggest that hepatic tuberculosis is more common in AIDS than previously recognized, and that liver specimens should be examined routinely for the presence of acid-fast bacilli.

Evidence of AIDS-related mortality in Mumbai, India.

From an estimated 85,200 HIV-infected individuals in Mumbai in 1997, at least 4120 excess deaths attributed to AIDS occurred among 15-54-year-olds. To prevent repetition of this excess in other parts of India, priority intervention programmes should be instituted quickly because the window of opportunity is closing quickly.

PIP: Evidence for AIDS-related mortality in Mumbai, India, is presented in this article. Data from the death registry of the Public Health Department were used to analyze deaths that occurred between 1987 and 1997. The observed number of deaths was substantially greater than the expected number of deaths beginning with 1990. From an estimated 85,200 HIV-infected individuals in 1997, at least 4120 excess deaths attributed to AIDS occurred among 15-54 year olds. The increasing mortality over the years is significant and observed in both sexes. Among men and women aged 25-44 years the excess number of deaths was largely due to tuberculosis and other causes including AIDS. During the 11-year period, the rates of tuberculosis-related death increased by 70-140%. Recognizing the fact that tuberculosis is the most common opportunistic infection among AIDS patients in developed countries, a significant proportion of tuberculosis-related deaths could also be AIDS-associated.

Pathology of the heart in acquired immunodeficiency syndrome.

The spectrum of cardiac lesions in patients with acquired immunodeficiency syndrome in India is not described. To determine the extent of involvement of the heart with this disease, an autopsy study of 52 subjects having acquired immunodeficiency syndrome was carried out. Multiple sections were obtained from different anatomical parts of each heart. Forty-eight of the 52 hearts showed subtle microscopic changes, the most common being myocardial atrophy (48 cases), lymphocytic pericarditis (38 cases), fibrinous pericarditis (1 case), pericardial fibrosis (1 case), lymphocytic myocarditis (29 cases) and myocardial fibrosis (7 cases). Cryptococcosis of the heart was noticed in two cases, while in one case toxoplasmic myocarditis was identified. In only one case clinical presentation of cardiac involvement (pericardial effusion) was noted, which indicates that in spite of the presence of significant pathology in the heart, overt cardiac manifestations are infrequently seen in patients with acquired immunodeficiency syndrome.

Toxoplasmosis of the central nervous system in the acquired immunodeficiency syndrome.

Acute encephalitis caused by Toxoplasma gondi was diagnosed at autopsy in 10 (20.4%) of the 49 patients. All patients had under lying immunodeficiency due to AIDS and showed selective involvement of central nervous system at autopsy. Sexual promiscuity was the risk factor in nine cases while one case had a history of blood transfusion. Diagnosis of toxoplasmosis was hampered by a lack of suspicion that Toxoplasma could be the agent causing necrotising encephalitis. The large number of cases of CNS toxoplasmosis appearing in AIDs patients emphasize the necessity of including toxoplasmosis in the differential diagnosis of encephalitis of unknown aetiology.

Clinico-epidemiologic features of granuloma inguinale in the era of acquired immune deficiency syndrome.

BACKGROUND AND OBJECTIVES: Granuloma Inguinale (GI) is an endemic sexually transmitted disease (STD) in India. With increasing prevalence of human immunodeficiency virus (HIV) among patients with STD at a clinic in Mumbai, a study was conducted to determine clinico-epidemiologic features of GI and HIV. GOAL: To determine possible interaction between GI and HIV. STUDY DESIGN: Prospective follow-up of 21 consecutive cases (GI in HIV-seropositive individuals) and 29 controls (GI in HIV-seronegative individuals) to determine time to heal. All cases and controls received a standard treatment regimen of erythromycin, 2 g po daily, under supervision until healing occurred. RESULTS: Although GI ulcers at recruitment were not significantly larger among HIV-seropositive individuals as compared with those seen among HIV-seronegative individuals (mean size 4.4 cm2 vs. 3.6 sq2; odds ratio [OR] 1.22, confidence interval [CI] .95, 0.63, 2.40; p = 0.52), the former took longer time to heal completely (mean 25.7 days vs. 16.8 days; OR 1.82, CI .95, 0.99, 3.36; p = 0.03) and tended to produce greater tissue destruction (as included in results). CONCLUSION: These findings are important because slow-healing GI ulcers with underlying HIV infection, which may be caused by their interaction, will lead to increased transmission of both the infections.

PIP: Infection with genital ulcer disease (GUD) facilitates the transmission of HIV. However, granuloma inguinale (GI), an endemic sexually transmitted disease (STD) in India, has been ignored as a cause of GUD. In the context of increasing prevalence of HIV infection among patients with STD at a clinic in Mumbai, a study was conducted to determine the clinico-epidemiologic features of GI and HIV, with the goal of identifying any possible interaction between the two. 21 consecutive cases of GI in HIV-seropositive individuals and 29 controls, HIV-seronegative individuals with GI, participated in the prospective follow-up study to determine how long it takes for GUD to heal. Healing was considered complete when total re-epithelization of the ulcer(s) was observed. All cases and controls received a standard treatment regimen of erythromycin under supervision until healing occurred. While the GI ulcers at recruitment were not significantly larger among HIV-seropositive individuals compared with those among HIV-seronegative individuals, the former took longer to heal completely; an average of 25.7 days compared to 16.8 days, respectively. The former ulcers also tended to produce greater tissue destruction. Slow-healing GI ulcers with underlying HIV infection can lead to the increased transmission of both infections.

Severe weight loss: the predominant clinical presentation of tuberculosis in patients with HIV infection in India.

BACKGROUND: Tuberculosis is endemic in India and its prevalence is reported to be increasing in patients with human immuno-deficiency virus (HIV) infection. Several factors, including the level of immune deficiency, influence the clinical presentation of HIV-associated tuberculosis. METHODS: Between April 1994 and April 1996, 1820 patients with confirmed HIV infection were studied for their clinical, radiological and laboratory parameters. Severe weight loss was observed as a frequent presenting complaint. Hence, a case-control analysis was performed using severe weight loss as the presenting criterion among HIV-seropositive patients. RESULTS: Of the 1820 patients with HIV infection, 410 (23%) presented with severe weight loss of > 10% of body weight within the preceding month. Of these 410 patients, 176 (43%) had tuberculosis, 94 (23%) had chronic diarrhoea, and 89 (22%) had recurrent fever. Among 176 patients with tuberculosis, the following types of HIV-associated tuberculosis were seen: 115/176 (66%) had pulmonary, 49/176 (28%) had extrapulmonary tuberculosis; of these 49 cases with extrapulmonary tuberculosis 33 (18%) had disseminated tuberculosis, and 12/176 (7%) had both pulmonary and extrapulmonary involvement. In the group as a whole, 45/176 (25%) cases had disseminated tuberculosis. Clinical features of HIV-associated tuberculosis in decreasing order of frequency were chronic fever, chronic cough, lymphadenopathy and hepatosplenomegaly. The Mantoux skin test was significantly anergic among patients with extrapulmonary and disseminated tuberculosis (p = 0.001). CONCLUSIONS: There was a significant correlation between severe weight loss and tuberculosis (RR 17.5), chronic diarrhoea (RR 12.8) and recurrent fever (RR 4.5). The diagnostic value of the Mantoux skin test among HIV-associated tuberculosis is reduced, more so among those with extrapulmonary and disseminated forms.

Cutaneous cryptococcosis and molluscum contagiosum occurring in the same lesion in a patient with AIDS.

Patients with acquired immunodeficiency syndrome (AIDS) are susceptible to a wide range of pathogens due to profound defect in cell-mediated immunity. The co-existence of different diseases within the same lesion is a feature of human immunodeficiency virus (HIV) infection. We describe co-existent cutaneous cryptococcosis and molluscum contagiosum in the same lesion in a patient with the acquired immunodeficiency syndrome.

Condom and nonoxynol-9 use and the incidence of HIV infection in serodiscordant couples in Zambia.

We aimed to measure the effectiveness of latex condoms and of nonoxynol-9 [N-9] spermicides, in preventing HIV transmission in heterosexual serodiscordant couples in Lusaka. Each couple was examined at clinic visits scheduled at 3-month intervals for one year or more per couple, or until seroconversion or discontinuation. Couples were given condoms and their choice of 3 N-9 products and advised to use both at every intercourse. Sexual exposure was ascertained from coital logs that recorded coitus and barrier method use. HIV serological testing was done at each clinic visit (ELISA and Western blot if positive). One hundred and ten discordant couples were followed for a mean of 17.6 months. Seventy-eight per cent of coital episodes were protected by condoms, 85% by spermicides and 6.4% were unprotected. Fourteen seroconversions occurred (8.7 infections per 100 couple-years [c-y]). The rate was higher among seronegative men than seronegative women. Among couples who reported using condoms at every intercourse the infection rate was 2.3/100 c-y, compared with 10.7/100 c-y among couples using condoms less consistently (rate ratio [RR] 0.2; 95% confidence interval [CI] 0-1.6). Among couples who reported using N-9 at every intercourse, the seroconversion rate was 6.9/100 c-y; among couples who reported less than full-time N-9 use, the rate was 8.9/100 c-y (RR 0.8; 95% CI 0.2-2.8). Among the subset of female seronegatives, the N-9 RR was 0.5 (95% CI 0.1-3.8). But when we calculated HIV rates according to N-9 consistency in coital acts when condoms were not used, there was no evidence of protection with higher N-9 use. Consistent use of latex condoms reduces the incidence of HIV infection, but the association between N-9 spermicides and HIV is less clear. The current study could not provide compelling data on the impact of N-9 spermicide use on risk of HIV infection. The study's small size, as well as the consistency of concurrent condom use, limited our inferences. Available spermicide products must be studied further.

PIP: The protective effect of consistent condom use against HIV transmission in HIV-serodiscordant couples has been documented. Unknown, however, is the anti-HIV effect of nonoxynol-9 use. This issue was addressed in a survey of 110 HIV-discordant couples from Lusaka, Zambia, who were willing to use condoms/spermicide, maintain a coital log, and return for follow-up visits every 3 months for at least 1 year. 80 of these couples (73%) had a seropositive man and 30 (27%) had a seropositive woman. The mean duration of follow-up was 17.6 months. Of the total of 15,148 recorded coital episodes, 10% were protected by condoms only, 17% by nonoxynol-9 only, 66% by both condoms and nonoxynol (according to the study protocol), and 6% were unprotected by any barrier method. Consistent barrier method use declined with duration of follow-up. There were 14 seroconversions (8.9 infections/100 couple-years), including 8 initially seronegative men and 6 initially seronegative women. Among couples who used condoms 0-50%, 51-75%, 76-99%, and 100% of the time, the seroconversion rates were 20.8, 10.1, 7.3, and 2.3/100 couple-years, respectively. Seroconversion rates were 6.9 and 8.9/100 couple-years among those reporting consistent and inconsistent use, respectively, of nonoxynol-9. Although this study failed to provide evidence that nonoxynol-9 use confers significant protection against HIV infection, its small size and the consistency of concurrent male condom use limited inferences.

Major differences in the spectrum of gastrointestinal infections associated with AIDS in India versus the west: an autopsy study.

The spectrum of bowel infections in patients with AIDS in India is not well characterized. To examine this spectrum of infections, an autopsy study of 49 subjects was carried out. Multiple sections were obtained from the gastrointestinal tract. A pathogenic organism was detected in 25 (71%) of 35 patients with diarrhea vs. 4 (29%) of 14 patients without diarrhea (P < .01). The most frequent pathogen was cytomegalovirus (in 13; 27%), followed by parasites (9; 18%), fungi (8; 16%) and Mycobacterium tuberculosis (7; 14%). This is the first autopsy study of patients with AIDS in the Indian subcontinent and shows important differences in the profile of their opportunistic infections compared with those of such patients in the West. These findings will help define the optimal diagnostic and therapeutic approaches to patients with AIDS, which, in view of the considerable budgetary restrictions in developing countries, should be targeted toward the pathogens most frequently identified in such areas.

Cryptosporidium, isospora and strongyloides in AIDS.

BACKGROUND: Diarrhoea is a common presentation in patients with AIDS. It occurs due to a number of parasites which are seldom seen in immunocompetent hosts. METHODS: Between January 1993 and July 1994, faecal specimens from 77 patients with AIDS presenting with diarrhoea of more than a month's duration were examined by direct wet mount microscopy of saline and iodine preparations and by the modified Ziehl-Neelsen stain. RESULTS: Cryptosporidium, Isospora and Strongyloides stercoralis alone or in combination were present in 29 of the 77 patients. CONCLUSION: The presence of these parasites highlights their pathogenic potential for immunocompromised patients with AIDS. Diarrhoea due to Isosporais responsive to treatment, hence their identification has therapeutic implications as well.

Spermicide acceptability among patients at a sexually transmitted disease clinic in Zambia.

OBJECTIVE: This study assessed the acceptability of three nonoxynol-9 spermicides among persons attending a sexually transmitted disease clinic in Lusaka, Zambia. METHODS: Spermicidal foam, suppositories, and foaming tablets were evaluated. Women (n = 114) and men (n = 150) attending an sexually transmitted disease clinic were enrolled. After each participant used two products, each for 2 weeks, consistency of use and acceptability were evaluated. RESULTS: At admission, most women (74%) and men (58%) were not using any family planning method. Moreover, most women (85%) and men (98%) had at least one sexually transmitted disease or genital infection. During the study, the proportion of coital episodes protected by spermicide use was high, yet loss to follow-up and discontinuation were also substantial. Discontinuation was frequently unrelated to acceptability. Women and men rated all three products positively along several acceptability parameters. Foam was the least desirable delivery system due to excess messiness. CONCLUSIONS: The results of this study suggest that it is feasible to distribute spermicides to women and men at increased risk for sexually transmitted disease and that the products will be used. Further research should be done among different populations and include other spermicidal delivery mechanisms.

Tuberculin sensitivity and HIV-1 status of patients attending a sexually transmitted diseases clinic in Lusaka, Zambia: a cross-sectional study.

A cross-sectional study to estimate the prevalence of latent tuberculosis (TB) in a group of Zambians at high risk of human immunodeficiency virus type 1 (HIV-1) infection and to examine the effect of HIV-1 infection on the tuberculin response was conducted in the University Teaching Hospital in Lusaka, Zambia during July to September 1990. Patients were selected from those presenting to the out-patient clinic for first referral with either sexually transmitted or skin disease. 268 adults were included in the study; 158 (59%; 95% confidence interval [CI] = 53-65%) were HIV-1 antibody positive. Of 82 HIV-1 negative participants who returned for Mantoux skin test reading, 51 (62%; 95% CI = 57-67%) had a positive test reaction (diameter > or = 10 mm) after receiving 2 units of RT-23 tuberculin. Of 106 HIV-1 positive participants who returned, only 32 (30%; 95% CI = 26-34%) had a diameter > or = 10 mm. Nine (28%) of the HIV-1 positive and Mantoux positive participants had large reactions > or = 30 mm, compared to 4 (8%) of the HIV-1 negative, Mantoux positive participants (P = 0.03). Results in the HIV-1 negative group indicated a prevalence of latent TB of 62% in this population. HIV-1 infection was associated with a much higher frequency of negative response to tuberculin and with a few large skin test responses. Thus, in populations where HIV seropositivity is high, Mantoux skin tests cannot be used to assess those with latent TB who might benefit from chemoprophylaxis.

PIP: A cross-sectional study of the Mantoux response and HIV-1 status of a sample of patients with sexually transmitted diseases and skin diseases in Lusaka, Zambia, sought to estimate the prevalence of latent tuberculous infection. The sample was selected from patients attending the sexually transmitted diseases/dermatology section at the University Teaching Hospital, Lusaka, Zambia, between July and September 1990. A questionnaire regarding socioeconomic factors, history of TB, contact with TB, location and documentation of bacillus Calmette-Guerin (BCG) scar(s) and history of BCG vaccination was completed, and a physical examination for acquired immune deficiency syndrome (AIDS) was carried out. The Mantoux result was recorded as the average diameter of induration, measured in 2 perpendicular directions by the pen and palpation method. A total of 158 patients (59%) were HIV-1 positive. Of the 66 women who took part, 46 (70%) were HIV-1 positive; of the 201 men, 112 (56%) were HIV-1 positive (p = 0.06). 232 patients had sexually transmitted diseases, the commonest being genital ulceration; 123/231 (53%) were HIV-1 positive. The remaining 36 patients had skin diseases, the commonest being herpes zoster; 32/36 (89%) were HIV-1 positive. Of the 267 patients remaining in the study, 193 (72%) returned to have their Mantoux test read, 188 within 48-72 h. 106 (67%) HIV-1 positive patients and 82 (75%) HIV-1 negative patients returned. Of the 82 HIV-1 negative patients, 51 (62%) had a Mantoux reaction or= 10 mm; 55 (67%) had a reaction or= 5 mm. Of the 106 HIV-1 positive patients, only 32 (30%) had a Mantoux reaction or= 10 mm; 35 (33%) had a response or= 5 mm. Comparing HIV-1 negative and HIV-1 positive participants gave a significant odds ratio of 3.85 for a Mantoux response or= 10 mm. Among the individuals with a Mantoux reaction or= 10 mm, 9/32 (28%) of HIV-1 positive participants had a megareaction or= 30 mm, while megareactions occurred in 4/51 (8%) of HIV-1 negative participants (odds ratio 4.6).