Sterility and antibacterial activity of some antibiotics sterilized by irradiation

Sterility and antibacterial activity of several antibiotics (including some penicillins and their salts, gramicidin and neomycin) subjected to sterilization by irradiation has been studied. The compounds in solid phase have been exposed to gamma irradiation in air atmosphere at room temperature, with a dose of 25 kGy, and afterwards they have been subjected to tests recommended by FP V (volume I, 1990) checking their sterility and activity. The results have shown that the majority of initial compounds have been to a slight degree contaminated by bacteria from the genera Bacillus and Micrococcus, the number of bacteria did not exceed 10(2) CFU, and fungi up to 10 CFU in 1 g of the compound. All compounds subjected to sterilization with a dose of 25 kGy were sterile and preserved the activity required by FP V. The decrease in activity observed for some compounds was always within the limits of FP specification. The results have proved that the penicillins analysed, gramicidin and neomycin can be sterilized by irradiation with a dose of 25 kGy, without any detrimental effect on their properties and antibacterial activity.     

Some aspects of arsenic toxicity and carcinogenicity in living organism with special regard to its influence on cardiovascular system,blood and bone marrow

This paper gathers data on the most current aspects of arsenic action, especially its influence on the cardiovascular system, blood and bone marrow. A potential carcinogenic mechanism of arsenic is also discussed. Arsenic is a potent toxicant that may exist in several valencies and in a number of inorganic and organic forms. Most cases of arsenic-induced toxicity in humans are due to exposure to inorganic arsenic, and there is an extensive database on the human health effects of common arsenic oxides and oxyacids. Exposure of humans living near hazardous waste sites may involve inhalation of arsenic dusts in the air, ingestion of arsenic in water, food or soil, or dermal contact with contaminated soil or water. The exposure to arsenic via the inhalation route is responsible for the increased risk of lung cancer, although respiratory irritation, nausea and skin effects may also occur. The oral route of exposure to arsenic predominates in the general population. The most common effects of arsenic ingestion are gastrointestinal irritation, peripheral neuropathy, vascular lesions, anemia, skin diseases, including skin cancer and other cancers of the internal organs like bladder, kidney, liver or lung. Relatively little information is available on the effects of direct dermal contact with inorganic arsenicals, but several studies indicate local irritation and dermatitis as the major ones.     

Effects of combination of cyclosporine with losartan or enalapril on kidney function in uremic rats

Long-term treatment with cyclosporine in solid organ transplantation has been shown to be associated with the development of hypertension and nephrotoxicity. Angiotensin-converting enzyme inhibitors have well-known nephroprotective properties and may prevent cyclosporine A (CYA)-induced hypertension. Angiotensin receptor 1 antagonists have similar properties. The purpose of this study was to investigate if losartan or enalapril could be administered with CYA to reduce its nephrotoxic effect in uremic rats. The studies were performed on the following groups of rats: group I--control; group II--control rats + losartan; group III--control rats + CYA; group IV uremic rats; group V--uremic rats + losartan; group VI--uremic rats + CYA; group VII--uremic rats + losartan + CYA, group VIII--control rats + enalapril; group IX--control rats + enalapril + CYA; group X - uremic rats + enalapril; group XI--uremic rats + enalapril + CYA. Pretreatment with CYA, losartan or enalapril in uremic rats resulted in a significant increase in urea and creatinine levels and a decrease in hematocrit. The same effect was observed when uremic rats were given CYA + losartan or CYA + enalapril. Pretreatment with losartan was associated with the increase in the level of CYA much higher than with CYA treatment alone. Similarly, pretreatment with enalapril resulted in a significant increase in CYA concentration in both groups of rats given CYA: uremic and non-uremic. Results of our study show that the treatment with cyclosporine and a combination of losartan or enalapril results in an increase in creatinine and urea levels and a decrease in hematocrit. Therefore, physicians should exercise caution, when they give losartan and enalapril to kidney allograft recipients treated with cyclosporine, particularly with impaired allograft function.     

Rapid desensitization of receptors for pituitary adenylate cyclase-activating polypeptide (PACAP) in chick cerebral cortex

Pituitary adenylate cyclase-activating polypeptide (PACAP38) potently stimulates cyclic AMP formation in slices of chick cerebral cortex. One- to fifteen-minute pretreatment of slices with 30 nM PACAP38 led to a time-dependent attenuation (when compared with values observed in the control tissue) of the cyclic AMP response produced by subsequent re-stimulation with 1 microM PACAP38. Concentration-response curve for restimulation with PACAP38 applied at 0.01-1 microM to tissue slices preincubated for 15 min with 30 nM PACAP38 revealed dose-dependent decreases in subsequent cyclic AMP responses by 16-37%. It is concluded that in chick cerebral cortex, the receptors mediating PACAP-driven cyclic AMP responses (PAC1 receptors) undergo rapid homologous desensitization.     

Prolonged treatment with glucocorticoid dexamethasone suppresses melatonin production by the chick pineal gland and retina

The chick pineal gland and retina synthesize melatonin in a circadian rhythm with high levels during the night. The rhythmic changes in the hormone production result predominantly from the fluctuation in the activity of serotonin N-acetyltransferase (AA-NAT), a penultimate and key regulatory enzyme in melatonin biosynthesis. The aim of this study was to analyze the effects of an acute and prolonged in vivo treatment with a glucocorticoid dexamethasone (4 mg/kg, ip) on the nocturnal increase in AA-NAT activity in chick pineal gland and retina. In acute experiments, dexamethasone (single dose)-injected chicks were killed after 2 h, while in prolonged experiments the glucocorticoid was given once daily for 7 days and the animals were killed 26-32 h after the last injection. Acute administration of dexamethasone did not affect AA-NAT activity in the chick pineal gland and retina. In the pineal glands and retinas of chicks that were treated with dexamethasone for one week and then killed at the end of the light phase of the 12:12 h light-dark cycle, AA-NAT activity was significantly higher than the enzyme activity found in tissues isolated from the vehicle-treated (control) animals. In addition to that, the nocturnal increase in pineal and, to a lower extent, retinal AA-NAT activity was significantly lower in dexamethasone-treated birds when compared with the respective control groups. It is suggested that prolonged treatment of animals with dexamethasone reduces the amplitude of the rhythmic melatonin production, a phenomenon which may affect chronobiological processes being under control of this hormone.     

Intrathecal baclofen in severe spasticity due to multiple sclerosis

Intrathecal administration of baclofen via programmable pump is a highly effective treatment method in severe spasticity resistant to oral medications. The authors describe a case of severe spasticity with tetraplegia and painful (> 10 a day) muscle spasms in the upper and lower limbs and paraspinal muscles, in a patient with clinically definite diagnosis of multiple sclerosis (MS). The 34-year-old female patient with a 15-year history of MS, suffering from lower limb spasticity with pes equinovarus since 1995, was treated with very good results with botulinum toxin injections of calf muscles (14 sessions of Dysport 1500iu till 2002). In the early 2002 she developed tetraplegia with severe, generalized and intractable spasticity. After 4 months of ineffective polytherapy (with high doses of oral baclofen, tizanidine, gabapentine, clonidine, diazepam) and the patient's enormous sufferings (she could neither sit up nor voluntarily change her position in bed), a programmable baclofen pump (Medtronic) was implanted. As soon as a few days after the surgery she could stand, sit and move voluntarily, her painful spasms disappeared, and her bladder catheter was removed. At a 6-month follow-up the effect was stable--she was able to walk a long distance outdoors with the aid of a crutch. The daily dose of the drug is 500 micrograms. No side effects of complications were noted.     

Significance of synaptic connectivity reduction for pathogenesis, clinical picture and course of schizophrenia

Synaptic connectivity disorders are significant in the pathogenesis of schizophrenia. Myelinization and abnormal function of oligodendroglia are the most important factors damaging synaptic connectivity. The main phase of the pathogenetic process leading to schizophrenia is the loss of synaptic connectivity below critical level, dependent on primary synaptic density (caused by genetic and perinatal factors), and on elimInation of synaptic connection during late adolescence and early adulthood. Various clinical pictures and courses of schizophrenia are related to various levels of synaptic density reduction. New imaging techniques (MRI, MTI, DTI) found many abnormalities in white matter--in myelin and oligodendroglia in schizophrenics. Actually, we don't know, whether these abnormalities are primary (caused by genetic factors) or secondary (caused by other factors, fox example by glutamatergic excitotoxicity of oligodendroglia).