Early deprivation leads to long-term reductions in motivation for reward and 5-HT1A binding and both effects are reversed by fluoxetine

Early life stress is a risk factor in aetiology of depression. In rats, early life stress can lead to pro-depressive biomarkers in adulthood. The present study in male Wistar rats investigated the effects of early life deprivation and fluoxetine on motivation for reward, activity in the forced swim test, and brain monoamine receptors, in adulthood. P1-14 pups were isolated for 4 h/day (early deprivation, ED) or were handled for 1 min (CON). They were weaned at PND21 and left undisturbed until 4-6 months old. The ED and CON groups were halved to receive either vehicle or fluoxetine (FLX, 10 mg/kg, 31 days). Thus, four treatment groups were studied: CON-VEH, CON-FLX, ED-VEH and ED-FLX, n = 8 each. On a progressive ratio schedule, ED-VEH animals showed significantly reduced motivation to obtain sucrose versus CON-VEH, and this reward-motivation deficit was reversed by FLX. Activity in the forced swim test was unaffected by ED and increased by FLX. Quantitative autoradiography was used to determine 5-HT1A and 5-HT2C receptor binding with [O-methyl-³H]WAY 100635 and [³H]mesulergine (added spiperone and 8-OH-DPAT), respectively. In ED-VEH versus CON-VEH, 5-HT1A receptor binding was significantly reduced in anterior cingulate, motor cortex, ventral hippocampal CA1 and dorsal raphé; this was reversed by chronic FLX. Concomitant ED-dependent reductions observed in 5-HT2C (motor and frontal cortices, ventral CA1 and dorsal raphé) and D2 (dorsolateral striatum and accumbens) binding were not reversed by FLX. Because chronic FLX treatment reversed the ED-induced behavioural and 5-HT1A binding deficits, the 5-HT1A receptor is implicated as a selective therapeutic target.     

Assessment of selected adhesion molecule and proinflammatory cytokine levels in the vitreous body of patients with type 2 diabetes — role of the inflammatory–immune process in the pathogenesis of proliferative diabetic retinopathy

Background  The aim of the study is to demonstrate the participation of the inflammatory-immune process in the pathogenesis of proliferative diabetic retinopathy (PDR). Methods  Twenty four women and 22 men with type 2 diabetes (mean age 63.97 ± 9.00 years, mean duration of diabetes 12.56 ± 6.87 years) were enrolled in the study. Serum concentrations of soluble forms of ICAM-1, VCAM-1 as well as IL-6 and TNF-α were evaluated in all study subjects. In 19 patients, simultaneous assessment of selected parameter levels in both serum and vitreous samples was performed. Vitrectomy was performed due to intravitreal hemorrhage, accompanied in some patients by traction retinal detachment. The control group consisted of 15 patients having undergone vitrectomy for reasons other than PDR. Tests were performed using the ELISA method. Results  Serum and intraocular concentrations of sICAM-1, sVCAM-1, IL-6, TNF-α were considerably higher in study subjects with PDR than in controls. Simultaneously, a positive correlation was found between intraocular sVCAM-1 (r = 0.590, p = 0.007), TNF-α (r = 0.822, p < 0.001) concentrations and HbA₁c levels. The above-mentioned dependence was not shown for sICAM-1 and IL-6 vitreous concentration. Local vitreous VCAM-1 level increase was also dependent on vitreous TNF-α concentration growth (r = 0.470, p = 0.043). No significant correlation was found between serum and vitreous levels of the selected parameters in the group of 19 patients with PDR. Conclusions  Increase in sICAM-1 and sVCAM-1 levels, as well as their correlation with high vitreous IL-6 and TNF-α concentrations in patients with PDR, seem to confirm the inflammatory–immune nature of this process. In diabetes, inadequate metabolic control remains an important risk factor in the development of PDR. We disclose commercial or similar relationships to products or companies mentioned in or related to the subject matter of the article being submitted. We have full control of all primary data and we agree to allow Graefe’s Archive for Clinical and Experimental Ophthalmology to review our data if requested.     

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.     

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).