Effect of total gamma-irradiation on the rate of steroid hormone hydroxylation by rat liver microsomes

gamma-irradiation in doses of over 600 r proved to decrease the rate of androgen hydroxylation significantly; the rate of hydroxylation of the estrogens under study altered but little. Under the mentioned irradiation conditions the content of cytochrome P-450 in rat hepatic microsomes diminished. A reduction of the hydroxylation rate of steroid hormones by rat hepatic microsomes under the effect of total gamma-irradiation apparently depended on the qualitative changes of cytochrome P-450.     

Effect of chronic anesthesia on the drug-metabolizing enzyme system and heme pathway regulation

Inadequate vascularization and microvascular rejection are major limitations for successful free pancreatic islet xenotransplantation. Commonly used immunosuppressive regimens may alter the process of vascularization, and are ineffective at preventing graft rejection. In this study, we investigated, in vivo, the action of the new immunosuppressive agent RS-61443 on angiogenesis and microvascular rejection of rat pancreatic islets after xenogeneic transplantation into the dorsal skinfold of Syrian golden hamsters. In nontreated xenografts, intravital fluorescence microscopy demonstrated a regular process of vascularization during the first 6 days after transplantation. On days 10, 14, and 20, graft rejection was observed, characterized by microvascular leukocyte accumulation (244+/-59 mm(-2)), loss of endothelial integrity, and capillary perfusion failure. Islet xenografts of animals treated with RS-61443 (40 mg/kg per day) demonstrated inhibition of vascularization with the consequence of a markedly reduced size of the grafts' microvascular network (0.05+/-0.007 mm2), when compared with that of nontreated xenografts (0.09+/-0.015 mm2; P< 0.05). However, treatment with RS-61443 effectively prevented microvascular graft rejection, as indicated by the absence of leukocyte accumulation (24+/-9 mm(-2); P<0.01), endothelial damage, and nutritive perfusion failure. Thus, RS-61443 treatment may represent an interesting approach for improving the outcome of pancreatic islet xenotransplantation.     

Ovariectomy-induced bone loss and the hematopoietic system

To investigate the relationship of the hematopoietic system to the loss of bone due to ovarian hormone deficiency, we examined the effects of ovariectomy and estrogen administration on the thymus, spleen and the bone marrow, and on the proliferation of marrow progenitors of osteoclasts. We also assessed the effects of daily administration of interleukin-1 receptor antagonist (IL-1ra) on bone loss due to ovarian hormone deficiency. Ovariectomy resulted in decreased cancellous bone volume, increased trabecular osteoblast and osteoclast numbers, and increased serum alkaline phosphatase levels that were prevented by 17 beta-estradiol treatment. Thymus weight, spleen weight, thymus and spleen lymphocytes, and bone marrow monocytes and lymphocytes also increased significantly following ovariectomy, and the increases were suppressed by 17 beta-estradiol. Ovariectomy, in addition, caused a 4-fold increase in the number of tartrate resistant acid phosphatase (TRAP)-positive multinucleated cells formed in cultures of marrow cells and the increase was partially inhibited by 17 beta-estradiol. IL-1ra administration did not prevent the bone loss due to ovariectomy. Our findings indicate that ovariectomy-induced bone loss in the rat is accompanied by marked changes in the hematopoietic system, and that these changes are modulated by estrogen administration. In spite of the negative finding with IL-1ra, the nature of the involvement of the hematopoietic system in the pathogenesis of bone loss due to ovarian hormone deficiency merits continued exploration.     

The occupational disease and injury compensatory system in the Czech Republic

Clinical manifestations of neonatal echovirus type 18 infections include a nonspecific febrile illness, diarrhea, and meningitis with or without exanthem. We report a successful outcome in a case of neonatal sepsis with shock caused by echovirus type 18, a complication not previously associated with this serotype.     

Effect of chronic experimental poisoning with benzene and ethylene vapors on the circulatory system

To examine the content and the composition of free amino acids in the intraluminal fluid of rat epididymis, the fluids were obtained by light pressure on the dissected tissues. The amount of the total free amino acids in the pressed fluid from the caput epididymis was significantly higher than those of the cauda epididymis and the testis. Glu and Gln were predominant amino acids in the caput, and their amounts occupied more than half of the total ninhydrin reactive compounds. Such a high concentration of Glu and Gln was not observed either in the cauda or in the testis. Castration decreased Glu and increased Gln in amount. Testosterone treatment to castrated animals did not restore Glu and Gln contents in the pressed fluid from the caput epididymis to the level observed in intact rats completely. Therefore, it was assumed that a large amount of Glu in the caput was due to many factors; secretion and metabolism of epithelial cells of the gland which might be regulated by androgen, inflow of rete testis fluid, and sperm metabolism of amino acids in the epididymis. The results obtained from the caput epididymis to which the efferent duct of the testis was ligated also supported this interpretation.     

Some preliminary observations on the effects of kola nut on the cardiovascular system

The prevalence of kola nut chewing and the effects attributed to it are briefly reviewed. Except for a generalisation that its effects are probably due to its caffeine content, no attempts have been made to quantify its specific actions. Preliminary observations on the cardiovascular system of the cat show that aqueous extracts of the nut evoke a dose dependent differential response - the 8 - 9% hypertensive effect of 0.01 ug - 1mg/ml doses contrasting with the 18--71% hypotensive response of 10--1000mgs/ml doses. Adrenergic receptor blockade showed no significant alteration of the response. With larger doses a bradycardia developed and cardiac arrythmias were observed as a terminal event. These results are compatible with the action of xanthines on the heart and peripheral vasculature. The possible role of the habitually chewed kola nut in the pathophysiology of cardiovascular disease and its implications have been briefly discussed.     

Apoptosis and therapy of malignant diseases of the hematopoietic system

Apoptosis is essential in the pathogenesis of hematological diseases. A tumor develops, if the balance between cell division and cell death is disturbed. In recent years many genes involved either in blocking or inducing this process have been identified. Additionally, several cytokines which influence apoptosis have been found. Some of these cytokines could also play a role in the development of resistance to chemotherapeutic agents. Many anticancer drugs exert their action via apoptosis. A strategy to selectively induce apoptosis of tumor cells without altering healthy cells and thus reducing the side effects of therapeutic regimens is a major goal for future development of new therapeutic techniques. Blocking the factors which are responsible for resistance is another promising therapeutic approach and could further improve the clinical outcome and finally prolong the life of patients.     

Complicated gastrointestinal bleeding of neoplastic diseases of the hematopoietic system

The incidence of gastrointestinal bleeding has been reported as 10-30% of the patients with neoplastic diseases of the hematopoietic organ. The pathogenesis of gastrointestinal bleeding is multifactorial; direct leukemic cell infiltrations mucosal changes ensuing from bone marrow suppression or immunodeficiency states, infections due to various organisms, and preceding peptic ulcers. Once the diagnosis of hematopoietic neoplasm has been established, complete gastrointestinal work-up by endoscopy, CT-scanning or MRI should be mandatory. Early examination of the gastrointestinal tract has advantages of recognition of preceding peptic ulcers and their treatment, as well as providing prophylactic steps to the gastrointestinal mucosa vulnerable to hemorrhage. The prognosis of gastrointestinal bleeding complicated with hematopoietic malignancies seems to be poor due to the fact that DIC, multiorgan failures or fatal infections are seriously involved in their terminal stages.     

Effects of chronic beta-blockade on compensatory mechanisms during acute isovolaemic haemodilution in patients with coronary artery disease

Gas embolism is a severe complication of laparoscopic surgery. We report two cases: one with lethal peroperative cardiac arrest from massive coronary artery gas embolism recognized during open-chest cardiac massage; the second case, also associated with coronary artery gas embolism, resulted in severe but transient abnormal left ventricular anterior wall motion, subepicardial ischaemia and injury in ECG leads V1 to V5, but unremarkable coronary arteriography and full recovery. The pathophysiology of gas embolism occurring during a laparoscopic procedure, the mechanisms of gas entry into the systemic vascular bed, the clinical, ECG, pulse oximetry, end-tidal CO2 concentration changes and alarm signs are discussed. The diagnostic value of Doppler transoesophageal echocardiography when possible is underlined, and emergency management of gas embolism is considered.     

Effect of chronic captopril treatment on circulating and tissue renin-angiotensin system in SHR rats

This study investigated spectral differences in the phonation of vowels between a group of 21 children with velopharyngeal impairment and a paired control group of 42 subjects. The speech material was composed of the isolated vowels /a/, /i/, and /u/, a sustained vowel /a/, and four vowels included in spoken words: two nasals /in/ and /on/ in "dindon," and two orals /a/ and /o/ in "gateau." A bottom-up discriminant function analysis indicated that the cepstrum coefficients and the linear-FFT were the most efficient tools in the test to classify the set of children. They were superior to the results obtained with the formant-representation of the vowels. The use of a perceptive scale (barks) did not improve the results. Discrimination over the total group showed percentages lower than those obtained when boys and girls were assessed separately. The best discriminating results were obtained with the /a/ of "gateau" for the girls and with the isolated /i/ for the boys.     

Effect of low-dose methylprednisolone on calcium balance and bone composition in rats

A rare case of Gorham's disease affecting the radius in a 46-year-old woman is presented. It was studied by plain radiography, MRI, and scintigraphy, including three-phase radionuclide bone scan and thallium scan. Three-phase bone scan demonstrated slightly decreased activity in the affected portion of the forearm in the early phase, but showed increased activity on the blood pool and delayed imaging. A thallium scan revealed no abnormalities. Histopathologic examination revealed osteoclastic activity and scar tissue with minimal remaining vasculature.     

Mobilization of hematopoietic progenitors in patients with chronic myeloid leukemia

Although the mobilization and harvesting of Philadelphia chromosome-negative progenitors has been proven feasible by a number of groups, it is not clear which techniques should be used with regard to the monitoring of purging and evaluation of stem cell yield. Therefore, we isolated CD34-positive cells from leukapheresis samples of seven CML patients after induction therapy. These cells were analyzed using the colony-forming unit granulocyte-macrophage (CFU-GM) and long-term culture-initiating cell (LTCIC) assays. In addition, we analyzed frequency and clonogenicity of single stem cells using the LTCIC assay at limiting dilution. Individual colonies derived from these assays were subsequently analyzed for the presence of the bcr-abl gene with interphase fluorescence in situ hybridization (FISH) and for the presence of bcr-abl mRNA with RT-PCR. We compared these results with the cytogenetic analysis of the leukapheresis material. Molecular analysis of individual colonies correlated well with the results of cytogenetic analysis. However, in nine out of 18 samples, cytogenetic analysis exclusively demonstrated the presence of either Philadelphia chromosome-positive or -negative cells whereas with the molecular analysis of individual colonies tumor contamination or the presence of residual normal cells could be substantiated. We concluded that molecular analysis of individual colonies should be employed to further optimize induction protocols. With regard to stem cell mobilization we demonstrated that about 67 CFU-GM colonies and clusters were generated by one single LTCIC both for the CML samples and the samples obtained from patients with non-hematologic malignancy. This number is important since until now most centres use a number of four colonies and clusters generated by one LTCIC. Dividing the CFU-GM output in the LTCIC assay by four to determine LTCIC frequency could thus lead to an almost 20-fold overestimation of the LTCIC frequency. It is concluded that stem cell frequency analysis is an important tool with regard to the interpretation of mobilization protocols.     

Effect of vitamin B6 on the side effects of a low-dose combined oral contraceptive

PURPOSE: To evaluate acquired color vision defects in glaucoma patients and glaucoma suspects. MATERIAL AND METHODS: 52 subjects (102 eyes) divided into four groups (with primary open angle glaucoma, normal tension glaucoma, ocular hypertension and with glaucoma-like optic disc) were examined with the IF-2 All-Color Anomaloscope. In all cases both the red-green equation of Rayleigh and the blue-green equation of Moreland were tested and three variables were determined: setting (matching) range (SR), calculated mid point (matching mid point) (CMP) and anomalous quotient (AQ) as compared to control group. RESULTS: No significant changes were found in the variables of the Rayleigh equation. However, in the blue-green equation SR was significantly enlarged in all tested groups and CMP was significantly shifted towards the short wavelength end of the match in first three groups. These results indicate a diminution of the color discriminating sensitivity in the short wavelength half of the visible spectrum and diminution of the blue cone sensitivity in glaucoma patients as well as in ocular hypertension (p < 0.001). In patients with glaucoma-like optic disc the setting range was enlarged in less degree (p < 0.01) without changes in the remaining variables (p > 0.05) what may be indicative of early stage of disease before the perimetric changes. CONCLUSION: Blue-green colour vision testing with the anomaloscope may serve as an additional test in the diagnostics of glaucoma. Glaucoma suspects with blue colour vision disturbances require the most careful investigation and if need be the recommendation of early treatment.     

The "cyclic" regimen of low-dose doxycycline for adult periodontitis: a preliminary study

Specially-formulated low-dose doxycycline (LDD) regimens have been found to reduce collagenase activity in the gingival tissues and crevicular fluid (GCF) of adult periodontitis subjects in short-term studies. In the current, double-blind, placebo-controlled study, adult periodontitis patients were administered for 6 months a "cyclical" regimen of either LDD or placebo capsules; and various clinical parameters of periodontal disease severity, and both collagenase activity and degradation of the serum protein, alpha 1-PI, in the GCF were measured at different time periods. No significant differences between the LDD- and placebo-treated groups were observed for plaque index and gingival index. However, attachment levels, probing depth, and GCF collagenase activity and alpha 1-PI degradation were all beneficially and significantly (P < 0.05) affected by the drug regimen. We propose: 1) that LDD inhibits tissue destruction in the absence of either antimicrobial or significant anti-inflammatory efficacy; and 2) that long-term LDD could be a useful adjunct to instrumentation therapy in the management of the adult periodontitis patient.     

Effect of low-dose acetazolamide on the ventilatory CO2 response during hypoxia in the anaesthetized cat

Acetazolamide, a carbonic anhydrase inhibitor, is used in patients with chronic obstructive pulmonary diseases and central sleep apnoea syndrome and in the prevention and treatment of the symptoms of acute mountain sickness. In these patients, the drug increases minute ventilation (V'E), resulting in an improvement in arterial oxygen saturation. However, the mechanism by which it stimulates ventilation is still under debate. Since hypoxaemia is a frequently observed phenomenon in these patients, the effect of 4 mg x kg(-1) acetazolamide (i.v.) on the ventilatory response to hypercapnia during hypoxaemia (arterial oxygen tension (Pa,O2)=6.8+/-0.8 kPa, mean+/-SD) was investigated in seven anaesthetized cats. The dynamic end-tidal forcing (DEF) technique was used, enabling the relative contributions of the peripheral and central chemoreflex loops to the ventilatory response to a step change in end-tidal carbon dioxide tension, (PET,CO2) to be separated. Acetazolamide reduced the CO2 sensitivities of the peripheral (Sp) and central (Sc) chemoreflex loops from 0.22+/-0.08 to 0.11+/-0.03 L x min(-1) x kPa(-1) (mean+/-SD) (p<0.01) and from 0.74+/-0.32 to 0.40+/-0.10 L x min(-1) x kPa(-1) (p<0.01), respectively. The apnoeic threshold B (x-intercept of the ventilatory CO2 response curve) decreased from 2.88+/-0.97 to 0.95+/-0.92 kPa (p<0.01). The net result was a stimulation of ventilation at PET,CO2 <5 kPa. The effect of acetazolamide is possibly due to a direct effect on the peripheral chemoreceptors as well as to an effect on the cerebral blood flow regulation. Possible clinical implications of these results are discussed.     

Neurotoxicity of chronic low-dose exposure to organic solvents: a skeptical review

The absolute configuration of the acyclic side chain of heptopyranosides and heptofuranosides was determined by exciton coupled CD, employing the strongly fluorescent 2-anthroate chromophore. The usage of this chromophore offers significant improvements over previous chemical and spectroscopic procedures since its intense fluorescence greatly facilitates the isolation and HPLC purification at the nanogram scale. The large amplitudes of the bisignate spectra allow CD manipulations in the 1 x 10(-7) M range.