Suppression of Oxidative Stress and Proinflammatory Cytokines Is a Potential Therapeutic Action of Ficus lepicarpa B. (Moraceae) against Carbon Tetrachloride (CCl4)-Induced Hepatotoxicity in Rats.

Local tribes use the leaves of Ficus lepicarpa B. (Moraceae), a traditional Malaysian medicine, as a vegetable dish, a tonic, and to treat ailments including fever, jaundice and ringworm. The purpose of this study was to look into the possible therapeutic effects of F. lepicarpa leaf extract against carbon tetrachloride (CCl4)-induced liver damage in rats. The DPPH test was used to measure the antioxidant activity of plants. Gas chromatography-mass spectrometry was used for the phytochemical analysis (GCMS). Six groups of male Sprague-Dawley rats were subjected to the following treatment regimens: control group, CCl4 alone, F. lepicarpa 400 mg/kg alone, CCl4 + F. lepicarpa 100 mg/kg, CCl4 + F. lepicarpa 200 mg/kg and CCl4 + F. lepicarpa 400 mg/kg. The rats were euthanized after two weeks, and biomarkers of liver function and antioxidant enzyme status were assessed. To assess the extent of liver damage and fibrosis, histopathological and immunohistochemical examinations of liver tissue were undertaken. The total phenolic content and the total flavonoid content in methanol extract of F. lepicarpa leaves were 58.86 ± 0.04 mg GAE/g and 44.31 ± 0.10 mg CAE/g, respectively. F. lepicarpa's inhibitory concentration (IC50) for free radical scavenging activity was reported to be 3.73 mg/mL. In a dose-related manner, F. lepicarpa was effective in preventing an increase in serum ALT, serum AST and liver MDA. Histopathological alterations revealed that F. lepicarpa protects against the oxidative stress caused by CCl4. The immunohistochemistry results showed that proinflammatory cytokines (tumour necrosis factor-α, interleukin-6, prostaglandin E2) were suppressed. The antioxidative, anti-inflammatory, and free-radical scavenging activities of F. lepicarpa can be related to its hepatoprotective benefits.

The potential protective effect of Commelina nudiflora L. against carbon tetrachloride (CCl4)-induced hepatotoxicity in rats, mediated by suppression of oxidative stress and inflammation.

BACKGROUND: This study aims to assess the hepatoprotective potential of Commelina nudiflora against CCl4-induced hepatic injury in rats. METHOD: Antioxidant activities were determined. Phytochemical analysis was performed by gas chromatography mass spectrometry (GCMS). In the in vivo study, Sprague Dawley rats were pretreated with C. nudiflora (150, 300, and 450 mg kg body weight (b.wt.)) once daily for 14 days followed by two doses of CCl4 (1 ml/kg b.wt.). After 2 weeks, the rats were sacrificed and hepatoprotective analysis was performed. RESULTS: In vitro studies have shown that the extract possessed strong antioxidant activity and has ability to scavenge 2,2-diphenyl-2-picrylhydrazyl-free radicals effectively. GCMS analysis of the C. nudiflora extract revealed the presence of various bioactive compounds. Administration of C. nudiflora significantly reduced the impact of CCl4 toxicity on serum markers of liver damage, serum aspartate transaminase (AST), and alanine transaminase (ALT). C. nudiflora also increased antioxidant levels of hepatic glutathione (GSH) and antioxidant enzymes and ameliorated the elevated hepatic formation of malondialdehyde (MDA) induced by CCl4 in rats. Histopathological examination indicated that C. nudiflora protect the liver from the toxic effect of CCl4 and healed lesions such as necrosis, fatty degeneration, and hepatocyte injury as irregular lamellar organization and dilations in the endoplasmic reticulum. The immunohistochemical studies revealed that pretreatment of C. nudiflora decreased the formation of 4-hydroxy-2-nonenal (HNE)-modified protein adducts and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Furthermore, overexpression of the proinflammatory cytokines TNF-α, IL-6, and prostaglandin E2 is also reduced. CONCLUSION: These findings exhibited the potential prospect of C. nudiflora as functional ingredients to prevent ROS-related liver damage.

Prenatal and postnatal exposure to diazinon and its effect on spermatogram and pituitary gonadal hormones in male offspring of rats at puberty and adulthood.

The objective of this research is to study the possible reproductive adverse effects of diazinon on rat offspring exposed in utero and during lactation. Twenty-four Sprague-Dawley female rats (10-12 week old) were randomly assigned to four groups, each consisting of six rats. Group 1 served as the control and these rats were given normal saline orally. Rats in groups 2, 3, and 4 were administered diazinon, dissolved in saline at 10, 15, 30 mg/ kg(-1) body weight, per oral, once daily, during mating, pregnancy and lactation. The male offsprings were examined at puberty and adulthood for body weight, testis weight, epididymis weight, sperm count, motility and morphology, pituitary-gonadal hormone levels. At 30 mg kg(-1) dose, the male offsprings showed a decrease in testicular weight, sperm count, motility, with an increase in abnormal sperm percentage and a decline in pituitary-gonadal hormones, at puberty. Upon attaining adulthood, there was a decrease in testicular weight, sperm count and motility with an increase in abnormal sperm percentage and a decrease in pituitary hormone level. There was evidence of some adverse reproductive effects on the male offspring at the 15 mg/ kg(-1) dose. Most of the adverse effects were irreversible and were evident at both puberty and adulthood in the offsprings, although a few parameters reverted to the normal growth pattern. Diazinon is a reproductive toxicant for male offsprings if exposed during prenatal and postnatal phases.

Association between Leptin (G2548A) and Leptin Receptor (Q223R) Polymorphisms with Plasma Leptin, BMI, Stress, Sleep and Eating Patterns among the Multiethnic Young Malaysian Adult Population from a Healthcare University.

Relative leptin resistance in childhood to absolute leptin resistance in maturity suggests sleep, eating behaviour, and the psychological state as probable causes. The current body of research provides inconclusive evidence linking G2548A and Q223R to obesity. Furthermore, we could find very little data that have observed the association between the environment and gene polymorphism, especially in the multiethnic population that exists in Malaysia. This study searched for a possible link between sleeping habits, eating behaviour, and stress indicators with plasma leptin and its genetic variation in young adult Malaysian healthcare students. The study involved 185 first- and second-year medical and dental students from a healthcare university. Polymerase Chain Reaction−Restriction Fragment Length Polymorphism(PCR-RFLP) determined the genotype, Enzyme Linked Immunoabsorbant Assay (ELISA) tested the serum leptin, and a self-administered questionnaire evaluated sleep, eating behaviour, and psychological condition. Gender and ethnicity are linked to fasting plasma leptin levels (p < 0.001). Plasma leptin also affects stress, anxiety, and sadness. Leptin (LEP) and Leptin Receptor (LEPR) polymorphisms were not associated with BMI, plasma leptin, sleep, eating behaviour, or psychological state. Young adult Malaysian Indians were obese and overweight, while Chinese were underweight. These findings imply overweight and obese participants were in stage I of leptin resistance and lifestyle change or leptin therapy could prevent them from becoming cripplingly obese as they age.

Dacarbazine induces genotoxic and cytotoxic germ cell damage with concomitant decrease in testosterone and increase in lactate dehydrogenase concentration in the testis.

Treatment of cancers with cytotoxic agents such as alkylating drugs often, but not always results in transient to permanent testicular dysfunction. The present study was planned to investigate the effects of dacarbazine [5-(3,3-dimethyltriazeno) imidazole-4-carboxamide] on testicular function in mice. Swiss albino mice (9-12 weeks old) were treated with 0, 5, 25, 50, or 100mg/kg body weight/day dacarbazine (i.p.) for 5 days at intervals of 24h between treatments. Mice were sacrificed on days 7, 14, 21, 28, 35, 49, and 70 after the last treatment (6 mice/dose/sample time), and the epididymal sperm count, sperm motility, sperm morphology, testicular histopathology (qualitative histopathology, seminiferous tubular diameter and epithelial height), and intra-testicular levels of testosterone and lactate dehydrogenase were assessed. Dacarbazine decreased the body weight only on day 28 at 25mg/kg dose-level, but increased the paired testes weights at 50mg/kg on day 7, at 25-100mg/kg on day 14, and at 25 and 50mg/kg on day 21 (P<0.05-0.01; one-way ANOVA and Bonferroni's post hoc test). The sperm count was decreased on all sampling days except at 5 and 25mg/kg dose-levels on day 70, but with severe oligospermia on days 28 and 35 (P<0.05-0.001). The sperm motility was decreased at 100mg/kg on days 14 and 21, at 5, 25, and 100mg/kg on day 28, and at all dose-levels on day 35 (P<0.05-0.001). Dacarbazine induced both head and tail abnormalities and some sperms with cytoplasmic droplets, but significant increase was seen in all dose groups on days 14 and 21, and at 100mg/kg dose-level on day 35. Drug-induced epithelial sloughing was seen on days 14-35 and other histopathological changes observed were vacuoles and abnormal cells. The STD was increased at 25-100mg/kg on day 7, at all dose-levels on day 14, at 50-100mg/kg on days 21 and 28, but without any effects on days 35-70 (P<0.05-0.001), and the tubular lumen was found dilated. The SE was increased on days 7, 21 and 28 at 100mg/kg and on day 14 at 50-100mg/kg. Dacarbazine reduced the intra-testicular testosterone level at 100mg/kg on day 7, at 5, 50 and 100mg/kg on day 14, at all dose-levels on days 21, 28, and 35, and at 50mg/kg on day 49 (P<0.05-0.001). The intra-testicular lactate dehydrogenase concentration increased at all dose-levels up to day 35, but without any effect on days 49 and 70 (P<0.05-0.001). There was no particular dose-response of dacarbazine on any parameters tested. The sperm count (except on day 7-positive correlation; Pearson product moment correlation) or sperm motility did not have any relation but increase in abnormal sperms showed negative correlation with decrease in testosterone level on days 7, 21 and 28. Decrease in sperm count was in negative correlation on days 14 and 35, and increase in abnormal sperms showed positive correlation on day 35 with increase in LDH level. Finally, the decrease in sperm motility had no correlation with increase in abnormal sperm shapes. We conclude that dacarbazine is genotoxic and cytotoxic to the mouse testis in a transient fashion, and these effects are exerted along with decrease in testosterone and increase in lactate dehydrogenase levels in the testis.

An organophosphate insecticide methyl parathion (o- o- dimethyl o-4-nitrophenyl phosphorothioate) induces cytotoxic damage and tubular atrophy in the testis despite elevated testosterone level in the rat.

Methyl parathion (MP) is an organophosphate pesticide used in agriculture, although quite often illegally used indoors to contain insects. The present study was planned to investigate the effects of MP on rat testis. Adult male Wistar rats (13-14 weeks) were treated with MP as follows. Experiment 1-0, 1.75, 3.5 or 7 mg/kg i.p. for 5 days and sacrificed on Day 14; experiment 2 and 3- 0, 0.5, or 1 mg/kg i.p. for 12 days, and sacrificed on Days 130 and 77, respectively; experiment 4- 0, 0.75, or 1.5 mg/kg i.p. for 25 days, and sacrificed on Day 17; experiment 5- 0 or 3.5 mg/kg po for 25 days, and sacrificed on Day 17, after the last exposure. MP decreased the body weight and the testis weight in experiments 4 and 5 (p<0.05-0.001) due to decreased food intake and tubular atrophy respectively. MP increased the intra-testicular testosterone level and decreased the LH level in experiments 4 and 5. The seminiferous epithelium showed sloughing of germ cells, vacuoles, focal necrosis, and formation of multinucleated giant cells, cellular degeneration (nuclear pyknosis, halo appearance and shrinkage of nuclei) and tubular atrophy, especially in experiment 4. The degree of testicular damage was higher in experiment 4>5>1>3>2 indicating more effect of prolonged i.p. treatment. Homogenization-resistant spermatid count was decreased in experiments 1, 4 and 5, and MP also decreased the tubular diameter, and epithelial height (p<0.05-0.001). Incidences of stage XIV tubules, number of meiotic figures and elongating spermatids were also decreased, whereas the incidence of tubules showing epithelial sloughing increased (p<0.05-0.001). We conclude that MP is a reproductive toxicant in male rats which causes significant testicular damage in the testis.

A broad-spectrum organophosphate pesticide O,O-dimethyl O-4-nitrophenyl phosphorothioate (methyl parathion) adversely affects the structure and function of male accessory reproductive organs in the rat.

Methyl parathion (MP) is an organophosphate pesticide used in agriculture, but also illegally used to spray homes and businesses to control insects. The present study was designed to investigate adverse effects of MP on accessory reproductive organs. Male Wistar rats aged 13-14 weeks were treated and sacrificed as follows. Experiment 1: 0.0 (water vehicle), 1.75, 3.5 or 7mg/kg (i.p.) for 5 days and sacrificed on day 14; experiment 2: 0.0, 0.5 or 1mg/kg (i.p.) for 12 days and sacrificed on day 130; experiment 3: 0.0, 0.5 or 1mg/kg (i.p.) for 12 days and sacrificed on day 77; experiment 4: 0.0, 0.75 or 1.5mg/kg (i.p.) for 25 days and sacrificed on day 17 and experiment 5: 0.0 or 3.5mg/kg (p.o.) for 25 days and sacrificed on day 17, after the last exposure. The accessory reproductive organs were removed, weighed and processed for histopathological analysis. Structural qualitative changes such as epithelial cell morphology and luminal observations were carried out for each organ in all experiments. Epididymis of one side was homogenized and biochemical estimations of acid phosphatase (ACP), cholesterol, total protein, uric acid, and Vitamin C were conducted by calorimetric methods in experiments 4 and 5. In experiment 1 the organ weights did not change; in experiment 2, the epididymal weight increased (P<0.001); in experiment 3, the weights of ductus deferens decreased at 1mg/kg and that of seminal vesicle decreased at both dose-levels (P<0.001). In experiments 4 and 5, weights of epididymis and prostate decreased, whereas in experiment 5, weights of ductus deferens and seminal vesicle increased (P<0.05-0.001). The sperm density was normal in control, moderately decreased in experiment 1 at 3.5 and 7mg/kg; in experiment 2 at 1mg/kg, and in experiment 5 at 3.5mg/kg, and severely decreased in experiment 3 at 1mg/kg and in experiment 4 at both dose-levels. The epithelial necrosis and nuclear pyknosis were seen in experiments 1, 3, 4 and 5, whereas nuclear degeneration was seen in experiment 1 and 4 and germ cells in the lumina of epididymis were seen in experiment 4. The nuclear pyknosis in the ductus deferens was seen in all experiments, except at 1.75mg/kg in experiment 1 and at 0.5mg/kg in experiment 3. Brush border disruption in the ductus deferens was seen in experiments 1 and 4; sperms were seen in the lumen in experiment 1 at 7mg/kg, and in experiments 4 and 5. The vacuoles in the epithelium were seen in experiments 1 and 4 and immature germ cells were seen in the lumen in experiment 4. The ACP and Vitamin C levels decreased in experiment 4 at both dose-levels, and in experiment 5 all biochemical parameters tested found decreased (P<0.01-0.001). The present results indicate that MP affects the structure and function of accessory reproductive organs in the rat.

Pathological review of breast lesions analyzed for estrogen receptor protein.

This report provides a detailed pathological review of 333 specimens analyzed for estrogen receptor protein (ERP) and correlates a series of morphological features with ERP results. Included were 147 primary breast carcinomas, 78 metastases, 27 fibroadenomas, and 81 nonneoplastic tissues, all from women. ERP in cytosols was assayed by incubation with [3H]estradiol in the presence and absence of "cold" estradiol followed by dextran-charcoal treatment. Results were summarized as positive (greater 60% inhibition by nontritiated estradiol, greater than 10 fmoles/mg protein), negative (less than 60% inhibition by nontritiated estradiol, less than 10 fmoles/mg protein), or intermediate borderline combinations. ERP in primary tumors ranged from 0.2 to 358 fmoles/mg protein (54.4% positive, 35.4% negative, 10.2% borderline). New findings are: (a) a high frequency of positive ERP in invasive lobular carcinoma (12 of 13, 92.3%) compared to typical ductal tumors (64 of 117, 54.7%); and (b) low frequency of positive ERP(5 of 21, 23.8%) in tumors with a prominent local lymphocyte reaction. Three ERP-positive noncarcinomatous specimens were fibroadenomas of high epithelial cellularity from patients under 30 years. No statistically significant relationship existed between ERP and any other morphological features that were examined.

Genotoxic and cytotoxic effects in the bone marrow of rats exposed to a low dose of paraquat via the dermal route.

The genotoxic effect of the herbicide paraquat was studied in rat bone-marrow by means of the micronucleus assay. Paraquat at dose levels of 6, 15 and 30 mg/kg body weight was given to rats in a single application via the dermal route. Marrow was collected at 24, 48 and 72 h after the application. The micronucleus assay was done as recommended by standard procedures. Paraquat gave rise to an increase in the number of micronuclei in a dose-dependent manner. The number of micronucleated polychromatic erythrocytes showed a maximum at 48 h and the toxicity was further prolonged, as there was no complete recovery at 72 h. These findings suggest a genotoxic effect of paraquat even after exposure via dermal application.

The antiviral drug ribavirin reversibly affects the reproductive parameters in the male Wistar rat.

The present study was planned to evaluate the toxic effects of ribavirin on the reproductive parameters in the male Wistar rat. Rats (11--13 weeks old) were treated with 5 injections (i.p.) of 20, 100 or 200 mg/kg/day ribavirin at intervals of 24 h. The testes were processed for histopathological analysis on days 14, 35, 70 and 105 after the last exposure. The parameters studied were body weight, the weights of the testis, epididymis, seminal vesicle and prostate, seminiferous tubular diameter (STD), epithelial height (SE), epithelial sloughing, incidence of stage XIV tubules, sperm abnormality and total serum level of testosterone. Data were analysed by ANOVA and the Bonferroni post hoc test for significances between different groups. There was a decrease in body weight and organ weights, excluding those of the testis and epididymis, against control at higher dose-levels. Ribavirin induced the formation of vacuoles, gaps and sloughing of the seminiferous epithelium. The STD, SE and the incidences of stage XIV tubules decreased on days 14 and 35. Ribavirin also induced the formation of sperm with microcephaly and cephalocaudal junction defects, with or without fibrils jetting out. All these morphological defects recovered to control limit by day 105. The serum level of testosterone was decreased at all dose-levels and time points, although recovery had started by day 105. In conclusion, ribavirin is gonadotoxic in male rats but the effects are reversible after a period of 105 days. However, the endocrine-disrupting properties of ribavirin persist beyond this period.

Prognostic significance of tumor emboli in intramammary lymphatics in patients with mammary carcinoma.

Approximately 20% of patients with invasive mammary carcinoma who do not have axillary metastases develop recurrent carcinoma within 10 years of initial therapy. There is clearly a need to identify those patients most likely to develop recurrences in this group since they may benefit from adjuvant therapy. This study was undertaken to evaluate the prognostic significance of intramammary lymphatic tumror emboli in patients with invasive breast carcinoma who did not have lymph node metastases. Twenty-three such patients treated in 1974 and 15 from 1964 were compared with matched groups of control patients who did not have lymphatic emboli. About 43% of patients with lymphatic emboli and 4% of those without emboli followed for 5 or more years in the 1964 group developed distant metastases (p less than 0.001). Local recurrences were found in only one study patient and one control in the entire series of 1964 and 1974 patients. The results suggest that among patients without axillary metastases, the finding of tumor cells in lymphatic spaces within the breast is associated with a substantial risk of distant metastases but not local recurrence.

Ceramic-on-polyethylene bearing surfaces in total hip arthroplasty. Seventeen to twenty-one-year results.

BACKGROUND: Polyethylene wear debris, and the resulting inflammatory response leading to osteolysis and loosening, is the primary mode of failure limiting the longevity of total hip replacements. Alternative bearing surfaces, including ceramic-on-polyethylene, have been investigated in an effort to decrease the amount of polyethylene wear debris. The purpose of this study was to evaluate the seventeen to twenty-one-year results of the use of ceramic-on-polyethylene total hip prostheses. METHODS: Sixty-four total hip prostheses were implanted with cement, by one surgeon, in fifty-six patients from 1978 to 1981. The average age at the index arthroplasty was sixty-nine years (range, fifty-one to eighty-four years). The components consisted of a cemented Charnley-Müller stem with a 32-mm modular alumina femoral head and a cemented all-polyethylene acetabular component. All patients who retained the index prosthesis were assessed clinically with use of Harris hip scores and were evaluated radiographically at the time of the latest follow-up. RESULTS: At the time of this latest follow-up, of the original sixty-four implants, eighteen (28%) were still in place and five (8%) had been revised. The remaining forty-one implants were in patients who had died and were functioning well until the patient's death. No patient was lost to follow-up. Of the eighteen hips with an intact prosthesis in the surviving patients, seven had an excellent clinical result; nine, a good result; and two, a fair result. One asymptomatic hip had definite radiographic evidence of femoral loosening. No hip had definite signs of acetabular loosening or evidence of osteolysis. Survivorship analysis revealed that the probability of survival of the prostheses without revision was 95% at five years, 95% at ten years, 89% at fifteen years, and 79% at twenty years. The mean linear and volumetric polyethylene wear rates were 0.034 mm/yr and 28 mm(3)/yr, respectively. There were no fractures of the ceramic heads. CONCLUSIONS: Outstanding long-term clinical and radiographic results were attained despite the use of what are now considered substandard techniques (an inferior stem design, a 32-mm head, and first-generation cementing techniques). The wear rates in this study are lower than previously reported metal-on-polyethylene wear rates and are consistent with the lowest reported in vivo ceramic-on-polyethylene wear rates. These findings support the consideration of ceramic-on-polyethylene bearing surfaces in total hip arthroplasty.

Ribavirin-induced sperm shape abnormalities in Wistar rat.

Ribavirin (1-beta-D-ribofuranosyl-1,2,4, triazole-3 carboxamide) is a broad-spectrum antiviral drug. This study was aimed to investigate the mutagenicity of ribavirin on germ cells by employing sperm morphology assay. Male Wistar rats were treated with water, cyclophosphamide (CP) 40 mg/kg, and ribavirin 20, 100 and 200 mg/kg (i.p.) for 5 consecutive days at intervals of 24h. Following the last exposure, at 14, 28, 35, 42 and 70 days, the epididymal sperm smears were obtained and stained according to the standard procedure. One thousand sperms per animal were classified into normal and different abnormal types. Both CP and ribavirin-induced anomalies of head and tail of sperm except at 70 days. In CP groups, maximum incidence was observed at 28, 35 and 42 days. Ribavirin 20 mg/kg induced maximum incidence at 14 and 42 days, 100 mg/kg at 28 and 42 days and 200 mg/kg at 28-42 days. These results show that ribavirin is mutagenic to rat germ cells in a transient fashion.

The genotoxic and cytotoxic effects of ribavirin in rat bone marrow.

The genotoxic and cytotoxic effects of the antiviral drug, ribavirin, was studied in rat bone marrow by employing the micronucleus assay. Ribavirin in doses of 10, 15, 20, 30, 50, 75, 100 and 200 mg/kg, and cyclophosphamide (CP) 40 mg/kg (only for sex-difference study) were injected intraperitoneally. Bone marrow was collected at 24 h and 48 h following the injection. To evaluate the recovery, the bone marrow was also sampled at 72 h from 20, 100 and 200 mg/kg treated rats. The micronucleus assay was conducted according to the standard procedure. Ribavirin elevated the incidence of micronuclei (except 10 mg/kg) in erythrocytes (P<0.01). The micronucleated polychromatic erythrocytes showed the initial steep increase at 15 and 20 mg/kg dose level, then with the gradual increase, possibly due to the limited metabolism and action of higher doses. The incidence of micronucleated normochromatic erythrocytes was not dose dependent. The effect was more at 48 h than 24 h due to prolonged toxicity of the drug or its metabolites, and by 72 h, recovery was observed even though the genotoxicity was significant. The PCE% decreased as the dose was increased up to 75 mg/kg, then without much difference between two higher doses. Only 100 mg/kg ribavirin and CP showed more toxicity on male rats. Cytotoxicity was seen due to hindered erythropoiesis or cell destruction. Our findings suggest that ribavirin is genotoxic and cytotoxic agent for rat bone marrow.

Effect of tamoxifen on spermatogenesis and tubular morphology in rats.

AIM: To observe the effect of tamoxifen citrate on spermatogenesis and tubular morphology in rats. METHODS: The effect of tamoxifen citrate i.g. at doses of 400 and 800 mg.kg(-1).day(-1) in 0.1 mL olive oil for 30 days on seminiferous tubular morphology, seminiferous epithelial diameter (STD), epithelial height (SEH), epididymal sperm count and percent abnormal sperm were evaluated at day 1, 12 and 36 after treatment. Controls were given the vehicle. RESULTS: The higher dose resulted in tubular atrophy on day 31. The STD, SEH and sperm count were decreased and the abnormal spermatozoa increased in a dose-dependent manner with the maximal effect on day 36. CONCLUSION: Tamoxifen citrate induces tubular shrinkage and atrophy and sperm abnormality at a dose-dependent manner.

Tamoxifen induced multinucleated cells (symplasts) and distortion of seminiferous tubules in rat testis.

AIM: To evaluate the effect of tamoxifen citrate on male reproductive system of rat. METHODS: Groups of male rats were gavaged with tamoxifen at doses of 200 mg x kg(-1) x d(-1), 400 mg x kg(-1) x d(-1) or 800 mg x kg(-1) x d(-1) in 0.1 mL olive oil for 10 consecutive days. Controls were treated with 0.1 mL olive oil. Rats were anesthetized and killed on d 3, d 15 or d 35 after the last dose. Testes were collected, processed for paraffin embedding, sectioned at 5 microm thickness, stained with HE and analyzed microscopically. RESULTS: There was a dose-dependent increase in the occurrence of seminiferous tubular distortion with germinal cell sloughing. The highest dose increased the number of multinucleated giant cells on d 3 and d 15. CONCLUSION: Tamoxifen citrate induces multinucleated giant cells and germinal epithelial sloughing in a dose-dependent manner and these changes are detrimental to male fertility.

Barr body distribution and estrogen receptor protein in mammary carcinoma.

The study was undertaken to investigate the relationship between Barr body distribution and estrogen receptor protein content of mammary carcinoma. The proportion of cells with one or more Barr body was determined in 105 specimens of mammary carcinoma from Guard stained imprints. Receptor protein content of the specimen was measured by the dextran charcoal method and compared with histopathologic features of the carcinomas. Primary carcinomas with Barr bodies in more than 10 percent of tumor cells were more likely to have higher levels of receptor protein than those with a lower proportion of Barr body containing cells (P less than 0.005). The results obtained for primary carcinoma may explain why patients with carcinomas that have a high proportion of Barr body positive cells are more likely to respond to hormonal therapy. Furthermore, these observations, when correlated with other available data about ERP suggest that an X-chromosome is involved in the synthesis of and/or carries the locus of action for estrogen receptor protein.

Emerging multiresistant strains: recommended precautions in the emergency room and surgical setting.

The current success in treatment of surgical site infections may be jeopardized by the continued emergence of antibiotic resistance in bacteria common to these infections. The effectiveness of vancomycin against methicillin-resistant staphylococci may decrease as more cases of VISA emerge. No currently available antimicrobial is consistently effective against certain strains of VRE and the potential emergence of VRSA. Orthopaedic surgeons soon may be in the undesirable position of having to eradicate organisms resistant to all available antibiotics. Several new antibiotics show promising activity and may be useful against these multidrug-resistant bacteria. However, as the history of bacterial resistance has taught us, it likely only will be a matter of time until these organisms adapt mechanisms of resistance to these new drugs. The key then lies, as it always has, in preventive measures. Surgeons, and all physicians, must adhere to the precautionary guidelines recently set forth by the CDC and HICPAC. Chief among these guidelines is the elimination of inappropriate antibiotic usage, especially inappropriate vancomycin use.

Mechanism of cytotoxicity of ribavirin in the rat bone marrow and testis.

Mechanisms of cytotoxicity of an antiviral drug, ribavirin was studied in the rat bone marrow and testis. Ribavirin at the dose levels of 20, 100 and 200 mg/kg was treated (i.p.) either as single (for bone marrow) or 5 (for testis) treatments. Bone marrow smears were obtained at 24, 48 and 72 h following the exposure and stained with the May-Gruenwald-Giemsa combination. Smears were screened for the incidence of dead cells, and at 24 h, a total of 2000 erythrocytes were counted to obtain the ratio of polychromatic erythrocytes (PCEs) to normochromatic erythrocytes (NCEs) (P/N). Step 19 spermatids/stage VII tubule, dividing cells (meiotic figures)/stage XIV tubule and the incidence of tubules with dead cells were counted in periodic acid--Schiff's reaction and haematoxylin (PAS-H) stained testicular sections on days 14, 35, 70 and 105. Significant decrease in the step 19 spermatids and meiotic figures, and increase in the incidence of tubules with dead cells (P < 0.05-0.01) were observed mainly on days 14 and 35. The cell death was observed in the bone marrow mainly at the two higher dose levels and significant decrease (P < 0.001) in P/N ratio was observed. This present study concludes that the cytotoxicity of ribavirin in these two target cell-lines in due to the induction of cell death and prevention of the cell division.

Effect of ribavirin on epididymal sperm count in rat.

Ribavirin (1-beta-D-ribofuranosyl-1, 2, 4-triazole-3-Carboxamide) is a potent inhibitor of inosine monophosphate dehydrogenase, used widely as an antiviral drug. Although it has been reported as a teratogen, its effect on spermatogenesis is not known. Male Wistar rats were segregated into 24 groups of 5 in each. Six groups were treated with water, 6 groups with 20 mg/kg, another 6 groups with 100 mg/kg and remaining 6 groups with 200 mg/kg for 5 days at intervals of 24 h (i.p.). Animals were anaesthetized at 14, 28, 35, 42, 70 and 105 days following the last exposure, laparatomy was conducted, epididymis was removed, minced in 1 ml phosphate buffered saline (PBS, pH 7.2), filtered and stained with 1% aqueous eosin Y. An aliquot was taken in haemocytometer, diluted in PBS and charged into Neubauer's chamber. Spermatozoa were counted in 8 squares except the central, and multiplied by 5 x 10(4). Data were analysed by Mann-Whitney "U" test. Ribavirin significantly decreased the sperm count in a dose and time dependent pattern and showed a recovery by day 105 except at 200 mg/kg. Ribavirin is reversibly cytotoxic to germ cells and decreases the production of spermatozoa.