Ultrastructural study on the hypothalamic-hypophysial-adrenal axis in fetal rats

The adrenal glands of decapitated and encephalectomized fetal rats were investigated electron microscopically and compared to those of normal intact fetal rats. Although the adrenal cortices did not show three zones (zona glomerulosa, fasciculata, and reticularis) on the 16.5th day of gestation when the decapitation or encephalectomy was carried out in utero, the zonation was recognized in fetuses operated on the 21.5th day of gestation. The same was true for normal control fetuses. However, cytoplasmic characteristics suggesting steroidogenesis in the cortical cells were reduced to various degrees in the encephalectomized or decapitated fetuses, especially in the latter ones. The change in cytoplasmic appearance was more conspicuous in the inner portion of the cortex. This result suggests that for the maintenance of normal adrenocortical function the hypothalamus may be indispensable even during the prenatal life of rats.     

Ultrastructural studies of spermiogenesis in rabbit exposed to chronic fluoride toxicity

OBJECTIVE: To compare skinfold thickness measurements with bioelectrical impedance analysis (BIA) as a measure of body fat for use in a survey of children (the National Study of Health and Growth). DESIGN: Part cross-sectional, part repeated measurement study. SETTING: A junior school in Bath. SUBJECTS: 42 boys and 33 girls aged from 9 to 11 years. INTERVENTIONS: Measurements of BIA, height, weight, and triceps, biceps, subscapular and suprailiac skinfolds. RESULTS: All measurements were highly repeatable with intraclass correlation coefficients > 0.90. The level of agreement between estimates of percentage of body fat derived from prediction equations based on impedance or skinfold measurements respectively was poor: the mean difference (impedance estimate minus skinfold estimate) was 4.67% (95% range -3.47 to 12.82) for boys and 7.81% (95% range 1.27 to 14.34) for girls. The two estimates were found to correlate highly (r = 0.83 for boys and r = 0.81 for girls) because weight, used to convert estimates of fat-free mass derived from impedance to fat mass, was highly correlated with impedance and moderately highly correlated with skinfold thicknesses. The correlations of resistance (R) and (H)2/R with skinfold thicknesses were very low. There was a moderate correlation of R and H2/R with log(weight-for-height index), but lower than that of log(weight-for-height index) with each of the skinfolds. CONCLUSIONS: As currently available equations for converting impedance-based estimates of total body water to fat mass are not fully developed for use in children of varying ages, estimates of body fat calculated from skinfold thickness measurements remain preferable in epidemiological studies of children's health and growth.     

Anxiolytic effects of cytotoxic hippocampal lesions in rats.

Rats with cytotoxic lesions of the hippocampus were given 3 anxiety tests: social interaction with a novel rat, the elevated zero-maze (a modification of the plus-maze), and hyponeophagia (eating familiar and novel foods in a novel place). Marked anxiolytic effects were seen in the social interaction and hyponeophagia tests, but not on the zero-maze. These results confirm and extend previous experiments that used traditional lesion techniques. The zero-maze result was consistent with other experiments using the plus-maze, in which intrahippocampal administrations of pharmacological agents were not anxiolytic, although variability in ethological tests may also be a factor. As the hyponeophagia test used an elevated apparatus, as in the zero- and plus-mazes, the lack of a lesion effect in the zero-maze was unlikely to have been due to an inability to relieve height-induced anxiety. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of cyclosporine on fertility in male rats

The effect of cyclosporine (CsA) on fertility has assumed greater importance with the increasing numbers of pediatric transplantations being performed all over the world. Conflicting reports on the effects of CsA on sex hormones are available. This experimental animal study was designed to examine the effect of CsA on testicular weight, sperm counts, seminiferous tubular diameter (STD), testicular morphology, DNA flowcytometry, sex hormone levels, and fertility in male rats. Those rats who received CsA (20 mg/kg per day) showed significant reductions in testicular weight (P < 0.05), sperm count (P < 0.01), Johnsen score (P < 0.05), STD (P < 0.01), serum testosterone levels (P < 0.05), haploid cell population (P < 0. 001) in the testis, and fertility (P < 0.001) compared to those receiving CsA 10 mg/kg per day and control rats. These findings will have an important bearing for children receiving cyclosporine for long periods to guide the physician in optimally adjusting long-term treatment.     

Conditioned cyclosporine effects but not conditioned taste aversion in immunized rats.

In 2 experiments, the development of adjuvant arthritis (an experimental autoimmune disease) was inhibited by exposing rats to a flavored solution that had previously been paired with injections of cyclosporine (an immunodepressive drug) compared with rats with the same history but exposed to a flavored solution that had previously not been paired with drug injections. In contrast to earlier experiments on conditioned cyclophosphamide effects, rats did not avoid the taste that had previously been paired with drug administration. Thus, conditioned immunopharmacologic effects were not confounded with taste aversion. These observations are interpreted as reflecting an associative learning process that affected the development of an autoimmmune disease. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A comparative study of anxiogenic effects of fluoroquinolones in rats

It is well known that the removal of a fixation point prior to the presentation of a peripheral target dramatically reduces saccadic reaction time (SRT). This effect has become known as the "gap effect". The present study examined several detailed kinematic variables to determine whether the removal of the fixation point also affects the manner in which saccades are produced. The findings indicate that saccades that were initiated after the removal of the fixation point had higher average velocities and reached greater peak velocities, accelerations, and decelerations than did saccades produced in the presence of the fixation point. The results suggest that the removal of the fixation point may affect the force-time curves of saccades in addition to affecting the time needed to initiate the saccades.     

Ultrastructural study of anti-tumor effects of tamoxifen in two malignant melanoma patients

In order to clarify the mode of action (tumor cell death) of tamoxifen in treatment for estrogen receptor (ER) negative malignant melanoma, we administered the usual adult dose (20 mg/day) or a low dose, 1/4 of the usual dose (5 mg/day), of tamoxifen for 2 months to 2 male patients and investigated ultrastructural changes in their melanoma cells from metastatic lesions before and after the treatment. After the 2-month administration, metastatic nodules in both patients were reduced in size by approximately 50%. Histologically, their reduced nodules presented coagulation necrosis around the blood vessels. Electron microscopy of the necrosis revealed that melanoma cells were degenerated and disappeared; numerous aggregated melanosomes, free melanosomes, granular endoplasmic reticula, and lysosomes were present in the extracellular matrix and in the space between collagen fibers. The remaining melanoma cells had swollen cytoplasm and mitochondria with vacuolar changes. Cristae of mitochondria had disappeared. There was no infiltration of lymphocytes into the nodules. The organic changes of necrosis lesions were not observed. Because our two patients were ER negative, these effects of tamoxifen could be attributable to an action not mediated by ER.     

Direct cytotoxic and cytoprotective effects of some drugs on isolated cells of gastric mucosa from rats

Toxic effect of ethanol and indomethacin, and the cytoprotective effect of prostacyclin were studied. In absence of other aggressive factors, the indomethacin was found to be non-toxic, but it could enhance the necrotizing effect of ethanol, this effect could be counteracted by prostacyclin preincubation. These observations suggest that there is an endogenous prostaglandin system in rat gastric mucosal cells that may protect against the toxic effect of indomethacin; administered prostacyclin may have a cytoprotective effect when this endogenous prostaglandin system's protective function does not more function. Gastric mucosal cytoprotection may include cellular level processes, which are able to operate without the existence of tissue integrity.     

Influence of neuroleptics on cytotoxic activity of macrophages in rats

The aim of the study was to evaluate the influence of neuroleptics on the in vivo and in vitro activities of rat spleen macrophages. In the in vivo study, three neuroleptics (chlorpromazine, haloperidol, and sulpiride) were given once, for 14 or 28 days. In the in vitro study, we evaluated the effects of two different concentrations of the neuroleptics on 3-day cultures of spleen macrophages. Rat spleen macrophages were isolated by the adherence method, and their cytotoxic activity was determined by measuring 51 Cr release from target cells P-815. In the in vitro study, both concentrations of all neuroleptics did not alter the cytotoxic activity of macrophages. In the in vivo study, neuroleptics (chlorpromazine 2 mg/kg, haloperidol 0.5 mg/kg, sulpiride 50 mg/kg) enhanced the cytotoxicity of macrophages both after a single injection and after 14 days. The results of the study indicate that the immunomodulatory effects of the neuroleptics depend mainly on dosage and experimental conditions.     

Increased natural killer resistance to cyclosporine A by continuous doses of dexamethasone in rats

There is a controversy on the effects of physiological levels of glucocorticoids on natural killer (NK) cytotoxity. Therefore, the effects of exogenously administered dexamethasone on NK cytotoxity in 8-week-old male, Fischer 344 rats were studied. We suppose that the reason for the controversy is insufficient sensitivity of the ordinal radioactive chromium-release assay for normal healthy subjects or animals. Therefore, we developed a new index, a resistance to artificial immunosuppressor, cyclosporine A (CsA) using rat NK activity as an indicator, and named this index, increased resistance to immunosuppressor (IRIS). After some basic, characterizing studies, authors confirmed the fact that continuous doses of dexamethasone (DEX) attenuated NK suppression of CsA. In protocol 4, 18 rats were randomly divided into three groups: the first (DEX + CsA) was injected for 5 days with 0.1 mg DEX/kg/day and a single dose of CsA on the final day, intraperitoneally; the second (SAL + CsA) was treated with an equal volume of saline and CsA; the third (DEX + SAL) was treated with DEX but not CsA. The IRIS in NK activity was increased significantly (P < 0.01) with 5 days injection of DEX. These results demonstrated that physiological, and continuous dosage of glucocorticoids stimulated IRIS in NK activity in rats, and this suggests that appropriate stimuli through the hypothalamic-adrenal axis might be acting, at least, as a defence against immune collapses or dysfunctions.     

Effect of cyclosporine on immune responses in submaxillary lymph nodes of pituitary-grafted rats

This work was undertaken to analyze the interrelationships between prolactin and cyclosporine in affecting immune responsiveness in submaxillary lymph nodes. Male rats received an anterior pituitary graft within breast muscles on day 5, or under the kidney capsule, on day 30 or 60 of life. On day 70 (rats operated on day 5 or 30) or on day 100 (rats operated on day 60) animals were injected with Freund's complete adjuvant and cyclosporine (5 mg/kg for 5 days), and were killed 2 days after immunization. Natural killer (NK) activity in submaxillary lymph node decreased in neonatally pituitary-grafted rats and increased in rats grafted on day 30 or 60, as did lymph node cellularity. Lipopolysaccharide (LPS)- and concanavalin A (ConA)-induced proliferation diminished in lymph nodes of rats grafted on day 30 or 60, respectively. Cyclosporine treatment diminished lymph node cell number and NK activity and increased the proliferative response to ConA. Cyclosporine depressive effect on lymph node cellularity was counteracted by the presence of a pituitary graft, as were the inhibition of NK activity and the stimulatory effect on ConA-induced cell proliferation. In pituitary-grafted rats, cyclosporine decreased submaxillary lymph node LPS-induced proliferation. Cyclosporine decreased the high circulating prolactin levels found in pituitary-grafted rats. The results are compatible with age-dependent, inhibitory and promoting activities of hyperprolactinemia on immune responses in lymph nodes, affected in a complex antagonistic and synergistic way by cyclosporine immunosuppression.     

Detection of cytotoxic effects of Clostridium novyi type A on bovine kidney cells

The cytotoxic effects of a toxic preparation from Clostridium novyi type A were demonstrated on tissue-cultured bovine kidney cells. The cytotoxic response was dose-dependent and could be neutralized by homologous antiserum. Scanning electron microscopy revealed damaged kidney cell surfaces. These findings indicated that the cytotoxicity may contribute to the formation of the foci in bovine tissue during an infection with C. novyi.     

Mechanistic study on liver tumor promoting effects of piperonyl butoxide in rats

Piperonyl butoxide, alpha-[2-(2-butoxyethoxy)ethoxy]-4,5-methylenedioxy-2-propyltol uene, is a widely used pesticide-synergist. Recently, results were reported indicating that piperonyl butoxide is a hepatocarcinogen in rat. Since the underlying mechanism was not elucidated, we examined the effects on rat liver cells in detail. For this purpose male F344 rats were administered piperonyl butoxide mixed in the diet at concentrations of 0 (negative control), 0.05, 0.2 or 2% for 2 days, 1, 2, and 4 weeks. As a positive control, phenobarbital was administered to rats for up to 4 weeks as a 0.1% solution in the drinking water. Increased liver weight, centrilobular hepatocellular hypertrophy due to increased smooth endoplasmic reticulum, decreased numbers and areas of connexin 32-positive spots per hepatocyte, and increased cell proliferation were observed in rats treated with 0.2 and 2% piperonyl butoxide. Similar results were obtained for 0.1% phenobarbital treated rats. Hepatocellular necrosis suggestive of hepatotoxicity was also observed in the 2% piperonyl butoxide group. These results indicate that the promoting mechanism of piperonyl butoxide in hepatocarcinogenesis is similar to that of phenobarbital, involving an ability to induce CYP isoenzymes and inhibit gap junctional intercellular communication. In addition, increased cell proliferation following hepatocellular necrosis may also play a role at high doses.     

Is there a beneficial effect of the calcium channel blocker diltiazem on cyclosporine A nephrotoxicity in rats?

To investigate whether or not there is a beneficial effect of diltiazem (D) on cyclosporine A (CsA) nephrotoxicity, renal function, CsA blood levels, and effects of CsA on biotransformation in the liver and on lipid peroxidation were characterized in rats. A single administration of D (60 mg/kg b.wt.) reduced urinary volume (UV), GFR and excretion of Na+ and K+, whereas a single dose of CsA (60 mg/kg b.wt.) alone had no respective effects. P-aminohippurate excretion was almost equal in all groups. Lower doses of D (and CsA) were without effects. After repeated CsA treatment a retardation in body weight gain was seen, with little effect of a co-administration with D hereon. In all tests, thymus mass was reduced by CsA, the weight of spleen, liver, adrenal glands, and kidney were not generally affected by any of the treatments. Furthermore, after repeated administration of CsA and/or D, urinary volume, GFR and Na+ excretion were reduced by CsA, too. Electrolyte concentrations in plasma showed no evident changes by any of the treatments for Na+ and Ca2+. After long time treatment, CsA and CsA + D quite similarly led to higher K+ but lower Mg2+ concentrations in plasma. Only with 7 days highest dosage treatment PAH excretion was reduced significantly by CsA and CsA + D treatment. Surprisingly, CsA levels measured in blood and in kidney tissue, showed lower values after co-administration with D compared to CsA treatment alone. This could be caused by higher activities of monooxygenase functions revealed after pretreatment with D alone. Reduced glutathione (GSH) contents in kidney were elevated in CsA and CsA + D treated groups. In general no significant differences were to be observed concerning lipid peroxidation and stimulated H2O2 formation. Altogether evident protective effects of diltiazem on CsA nephrotoxicity in rats could not be proven.     

The effects of cytotoxic perirhinal cortex lesions on spatial learning by rats: A comparison of the dark Agouti and Sprague-Dawley strains.

The effects of perirhinal cortex lesions in rats on spatial memory might depend on the choice of strain. The present study, therefore, compared perirhinal lesions in Sprague-Dawley rats (associated with deficits) with Dark Agouti rats (associated with null effects). Tests of reference memory and working memory in the water maze failed to provide evidence that perirhinal lesions disrupt overall levels of performance (irrespective of strain) or that these lesions have differential effects on the rates of spatial learning in these 2 strains. Strain differences were, however, found, as the Dark Agouti strain was often superior. Furthermore, the perirhinal lesions did have differential effects in the 2 strains, but these did not appear to relate directly to changes in spatial learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Different effects of cyclosporine or tacrolimus on hepatocyte acute phase proteins

We describe the MR findings in a patient with acute renal injury after blunt abdominal trauma associated with perinephric hematoma and urinoma. Both CT and MR findings are described. Active urine extravasation into a perinephric urinoma is demonstrated by serial post-contrast imaging with CT and MRI showing progressively increased attenuation/signal intensity fluid in communication with the collecting system, commencing 2 minutes after contrast administration.     

Manometric study of the effects of experimental fundoplication in rats

BACKGROUND: The manometric effects of surgical repair of gastroesophageal reflux remain largely unknown, making the interpretation of the changes in the esophagogastric high pressure zone after fundoplication difficult. AIM: To measure in a murine model the transdiaphragmatic pressure gradients, intraabdominal esophageal length, and lower esophageal sphincter pressure and length after Nissen fundoplication. MATERIAL AND METHODS: Adult Wistar rats were divided into two groups Control group (n = 10): in which measurements were made after laparotomy and intraabdominal esophageal dissection. Nissen Group (n = 15): in which measurements were made at baseline, after fundoplication and 1 week after surgery. We considered the following variables: end-inspiratory and end-expiratory transdiaphragmatic gradient (TDIG and TDEG respectively), lower esophageal sphincter pressure (LESP) length (LESL), and length of the intraabdominal segment of the esophagus (LIAS). RESULTS: The LIAS increased significantly after esophagogastric dissection in the control group (11.38 +/- 3.22 mm vs 16.02 +/- mm, p < 0.05). No differences between pre- and postoperative status were found in TDIG, TDEG, LESP and LESL in the control group. However, LESP increased significantly after fundoplication (14.22 +/- 13.3 vs 32.96 +/- 7.8 mmHg, p < 0.05) and these differences were still present one week later (30.72 +/- 6.73 mmHg, p < 0.05). LESL was also increased (1.91 +/- 1.76 mm vs 7.68 +/- 1.83 mm) after fundoplication (p < 0.05), and reached 7.02 +/- 2.18 mm (p < 0.05) 1 week later. No differences were found in pre- and postoperative TDIG, TDEG and LIAS in the Nissen Group. CONCLUSION: In this murine experimental model, intraabdominal esophageal dissection increased the length of the intraabdominal esophagus without modifying the esophagogastric high pressure zone, while Nissen fundoplication increased lower esophageal sphincter pressure and length, without modifying the length of the intraabdominal esophagus or the transdiaphragmatic pressure gradients.