Reproductive toxicity of carbofuran to the female mice: effects on estrous cycle and follicles

Carbofuran, a systemic N-methyl carbamate pesticide was orally administered with the doses of 0.4, 0.7, 1 and 1.3 mg/kg body weight/day to normal virgin female Swiss albino mice for 30 days. The vaginal smear and body weight of mice were recorded daily and mice were sacrificed on the 31st day. Estrous cycle was effected by showing a significant decrease in the number of estrous cycle and the duration of each phases of estrous cycle with concomitant significant increase in the diestrus phase in 1 and 1.3 mg/kg/d carbofuran treatment when compared with that of control mice. There was a significant decrease in the number of healthy follicles and a significant increase in the number of atretic follicles in 1 and 1.3 mg/kg/d treated groups when compared with the control. The histologic observations of the ovary revealed the presence of less number of healthy follicles and more number of atretic follicles in high dose of carbofuran treated mice. There was a dose dependent decrease in the body weight. The ovary weight was also decreased significantly in 1.3 mg/kg/d carbofuran treatment. There were no significant change in the weight of the organs such as uterus, kidney, adrenal, liver, spleen, thymus and thyroid. These observed effects of carbofuran on the estrous cycle and follicles may be due to a direct effect on the ovary or the hypothalamo-hypophysial ovarian axis causing hormonal imbalance.     

Effect of different schedules and efficacy of progesterone on implantation in dimethoate treated albino mice

Dimethoate, an organophosphorus pesticide, was administered orally at a dose of 28mg/(kg body weight day) to nulliparous pregnant albino mice on day 3 only and for days 3, 5 and 7 to examine the possible mechanisms for the time dependent and efficacy of progesterone on implantation in dimethoate treated animals. Control mice received similar quantities of distilled water. Autopsy on day 8 revealed that the distilled water treated mice were pregnant and had a normal number of implantations and a normal duration of diestrus. Treatment with dimethoate on day 3 only and for days 3 pregnancy caused a partial inhibition of implantation wherein 6 and 4 out of 10 mice were pregnant with 68.04 and 83.69% pre-implantation loss, respectively. However, treatment with 28mg/(kg body weight day) dimethoate for days 5 and 7 caused complete inhibition of implantation in all the mice with 100% pre-implantation loss and the uterus showed no implantations. There was a significant decrease in the body weight, ovaries and uterine weights in 28mg/(kg body weight day) dimethoate treatment for days 7 of pregnancy in mice as there was complete inhibition of implantations. These groups exhibited an increase in the estrus phase. However, there was no significant change in the weight of other organs in dimethoate treated mice. Inhibition of implantation by dimethoate may be due to imbalance in the estrogen:progesterone ratio, essential for implantation. Based on this hypothesis 4, 9 and 12mg/(kg body weight day) progesterone was administered subcutaneously along with 28mg/(kg body weight day) of dimethoate for days 7 of pregnancy to counteract the effect of dimethoate and to maintain the implantations. Mice treated with 4, 9 and 12mg/(kg body weight day) progesterone along with 28mg/(kg body weight day) dimethoate for days 7 of pregnancy was unable to maintain the implantation with the result there was a 100% pre-implantation loss. There was a significant decrease in the body weight with all the dimethoate and progesterone treated mice. However, uterine weight was significantly decreased with 12mg/(kg body weight day) progesterone along with dimethoate treated mice when compared to controls.     

Diagnostic yield of blood clot culture in the accurate diagnosis of enteric fever and human brucellosis

Culture of blood is the most frequent, accurate means of diagnosing bacteremia in enteric fever and brucellosis. However, conventional blood culturing is slow in isolating bacteria causing these diseases. In this work, we evaluated the performance of blood clot culture and conventional whole blood cultures in the accurate diagnosis of enteric fever (253 cases) and human brucellosis (71cases). The blood clot culture was found to be much more sensitive for both Salmonella (more by 34.4%, P< 0.001) and Brucella (more by 22.6%, P<0.001) than whole blood culture. Bacterial growth was significantly faster in cultures of blood clot compared to whole blood (1.1 versus 2.6 days for Salmonella, 3.1 versus 8.2 days for Brucella melitensis, respectively). The rapid confirmation of the etiological agent would facilitate an early institution of appropriate antimicrobial therapy, thereby reducing clinical morbidity especially in an endemic population. It is worthwile practicing blood clot culture for the accurate diagnosis of enteric fever and brucellosis in developing countries where diagnostic facilities by advanced technologies like automated culture systems and PCR are not available.     

A study of morbidity pattern among prostitutes attending a municipal clinic in Pune

The findings of the present study revealed that out of 200 prostitutes attending a clinic for various ailments, 81.50% were suffering from sexually transmitted diseases (STD) thus posing a potential risk of transmitting these diseases to their clients. Syphilis was found to be the commonest STD afflicting 36.80% of the respondents, the next common being the chancroid (31.28%); 5.52% of the respondents were found to be suffering from concomitant venereal infections. The other important communicable diseases with which some respondents were found to be afflicted, included--tinea infection (3 cases), scabies (2 cases), leprosy (2 cases), pulmonary tuberculosis (4 cases) and upper respiratory tract infection [3 cases). Thus, the prostitutes remain an undisputed potential source of infection not only of STDs but also several other communicable diseases. Therefore, their continuous surveillance, early diagnosis, appropriate treatment and subsequent follow-up should be meticulously carried out. On the other hand the public, particularly the sexually promiscuous individuals must be imparted vigorous health education to avoid exposure to this source.     

Synthesis, characterization, antimicrobial and single crystal X-ray crystallographic studies of some new sulfonyl, 4-chloro phenoxy benzene and dibenzoazepine substituted benzamides

A new class of benzamide derivatives 3a(I-VI) and 3b(I-VI), bearing different bioactive moieties were synthesized and evaluated for their efficacy as antimicrobials in vitro. Compounds 3bVI, 3aII, 3aV, 3bIII, 3aVI, 3bII showed significant antibacterial activity and 3bIII, 3bII, 3aIV, 3bV, 3bVI, 3aI exhibit significant antifungal activity. The title compounds are characterized by spectral and elemental analysis. Compounds 2-methoxy-N-[4-(thiazol-2-yl-sulfamoyl)-phenyl]-benzamide 3aII and 2-(2-(2-ethoxybenzoylamino) phenethyl)-N-(2-ethoxybenzoyl) benzenamine 3bV are characterized by the single crystal X-ray studies. Compound 3aII crystallizes in monoclinic space group P2(1) and 3bV in triclinic space group P-1. Compounds 3aII and 3bV exhibit both inter and intra molecular hydrogen bonding.     

Hydroxychloroquine is a safe and effective steroid-sparing agent for immune checkpoint inhibitor–induced inflammatory arthritis

Clinical Rheumatology - Immunotherapy for cancer treatment continues to evolve, and immune checkpoints have proven successful therapeutic targets. With success has come the challenge of managing...     

The impact of tumor burden characteristics in patients with metastatic renal cell carcinoma treated with sunitinib

BACKGROUND:

An important goal of noncurative therapy for metastatic renal cell carcinoma (mRCC) is tumor burden (TB) control. However, to the authors' knowledge, the impact of TB characteristics on clinical outcome has not been studied in patients with mRCC who were treated with vascular endothelial growth factor‐targeted therapy.

METHODS:

Patients with clear cell mRCC who were treated with sunitinib between June 2004 and October 2007 were retrospectively identified. Computed tomography scans were re‐reviewed from baseline, at the time of maximal TB shrinkage (TS) while receiving sunitinib, and at the time of progressive disease (PD). Measurements were recorded as per Response Evaluation Criteria In Solid Tumors (RECIST).

RESULTS:

A total of 69 patients were identified. The majority (54%) were classified as being of favorable risk using Cleveland Clinic Foundation Tyrosine Kinase Inhibitor (CCF TKI) risk group criteria. All patients underwent prior nephrectomy and 77% received prior systemic therapy. There were a median of 8 metastatic deposits across all organs (range, 1‐27 deposits). The median TB at the initiation of therapy was 14.0 cm (range, 3.0 cm‐42.2 cm). On multivariable analysis, baseline characteristics of disease confined to above the diaphragm (P = .03) and a total TB <13 cm (P = .09) were found to be independent positive predictors of progression‐free survival. A+ baseline, total number of metastases <10 (P < .001) and TB above the diaphragm <6.5 cm (P = .05) were found to be independent positive predictors of overall survival (OS). Increased TS while receiving sunitinib was found to be significantly associated with OS (P < .001). At the time of PD, tumor location and pattern of disease progression were not found to be associated with survival as measured from the date of PD. However, total TB (P = .003) and total number of metastatic deposits (≤12 vs >12; P < .001) were found to be significant predictors of survival after PD.

CONCLUSIONS:

The results of the current study indicate that TB characteristics are associated with clinical outcome in patients with mRCC who are treated with sunitinib. Cancer 2011. © 2010 American Cancer Society.