Environmental enrichment reverses behavioral alterations in rats prenatally exposed to valproic acid: issues for a therapeutic approach in autism.

Environmental enrichment has been repeatedly shown to affect multiple aspects of brain function, and is known to improve cognitive, behavioral, and histopathological outcome after brain injuries. The purpose of the present experiments was to determine the effect of an enriched environment on behavioral aberrations observed in male rats exposed to valproic acid on day 12.5 of gestation (VPA rats), and proposed on the basis of etiological, anatomical, and behavioral data as an animal model of autism. Environmental enrichment reversed almost all behavioral alterations observed in the model. VPA rats after environmental enrichment (VPA-E) compared to VPA rats reared in standard conditions have higher sensitivity to pain and lower sensitivity to nonpainful stimuli; stronger acoustic prepulse inhibition; lower locomotor, repetitive/stereotypic-like activity, and enhanced exploratory activity; decreased anxiety; increased number of social behaviors; and shorter latency to social explorations. In comparison with control animals (Con), VPA-E rats exhibited increased number of pinnings in adolescence and social explorations in adulthood, and were less anxious in the elevated plus maze. Similar differences in social behavior and anxiety were observed between control rats exposed to environmental enrichment (Con-E) and control group reared in standard conditions. These results suggest that postnatal environmental manipulations can counteract the behavioral alterations in VPA rats. We propose environmental enrichment as an important tool for the treatment of autism spectrum disorders.     

The influence of saturated fatty acids on prostaglandin synthetase activity

Saturated fatty acids (C₁₀, C₁₂, C₁₄, C₁₆ and C₁₈) as well as lauryl sulphate inhibit the microsomal prostaglandin synthetase of bovine seminal vesicles (BSVM). The most potent inhibitors are lauryl sulphate, lauric and myristic acids ($\text{ic}{}_{50}\text{= 250 μ}\text{M}$). The last two acids are strong ligands to hydrophobic sites of albumin. Indomethacin is also strongly bound to the hydrophobic sites of albumin; however, indomethacin inhibits the generation of prostaglandins at a concentration approximately 2500 times lower than the most active fatty acid inhibitor. The inhibitory action of fatty acids and indomethacin on prostaglandin synthetase activity has been measured by estimation of either PGE₂ or malondialdehyde, which are generated from arachidonic acid by BSVM. The former procedure is more reliable and reproducible than the latter.     

Opioids in neuropathic pain

Opiates lack potent analgesic efficacy in neuropathic pain although it is now generally accepted that the poor effect of these drugs reflects a reduction in their potency. Reduction of morphine antinociceptive potency was postulated to be due to the fact that nerve injury altered the activity of opioid systems or opioid specific signaling. Endogenous opioid systems were found to be represented in the regions involved in the nociception and are implicated in chronic pain. Opioid peptides biosynthesis and opioid receptors density in the nociceptive pathways and their functions change under various conditions associated with neuropathic pain following damage to the spinal cord and injury of peripheral nerves. Identification of a role of opioid systems in neuropathic pain and molecular and cellular mechanisms underlying these processes are of importance to understanding of the opioid action in neuropathic pain that will hopefully facilitate development of therapeutic strategies in which effectiveness of opioids in alleviation neuropathic pain is increased.     

Nitrite infusions to prevent delayed cerebral vasospasm in a primate model of subarachnoid hemorrhage

Context  Delayed cerebral vasospasm causes permanent neurological deficits or death in at least 15% of patients following otherwise successful treatment for ruptured intracranial aneurysm. Decreased bioavailability of nitric oxide has been associated with the development of cerebral vasospasm. Objective  To determine whether infusions of nitrite will prevent delayed cerebral vasospasm. Design, Setting, and Subjects  A total of 14 anesthetized cynomolgus monkeys had an autologous blood clot placed around the right middle cerebral artery. Cerebral arteriography was performed before clot placement and on days 7 and 14 to assess vasospasm. The study was conducted from August 2003 to February 2004. Interventions  A 90-mg sodium nitrite intravenous solution infused over 24 hours plus a 45-mg sodium nitrite bolus daily (n = 3); a 180-mg sodium nitrite intravenous solution infused over 24 hours (n = 3); or a control saline solution infusion (n = 8). Each was infused continuously for 14 days. Main Outcome Measures  Nitrite, S-nitrosothiol, and methemoglobin levels in blood and cerebrospinal fluid and degree of arteriographic vasospasm. Results  In control monkeys, mean (SD) cerebrospinal fluid nitrite levels decreased from 3.1 (1.5) µmol/L to 0.4 (0.1) µmol/L at day 7 and to 0.4 (0.4) µmol/L at day 14 (P = .03). All 8 control monkeys developed significant vasospasm of the right middle cerebral artery, which was complicated by stroke and death in 1 animal. Sodium nitrite infusions increased the nitrite and methemoglobin levels (<2.1% of total hemoglobin) in the blood and cerebrospinal fluid without evoking systemic hypotension. Nitrite infusion prevented development of vasospasm (no animals developed significant vasospasm; mean [SD] reduction in right middle cerebral artery area on day 7 after subarachnoid hemorrhage of 8% [9%] in nitrite-treated monkeys vs 47% [5%] in saline-treated controls; P<.001). There was a negative correlation between the concentration of nitrite in cerebrospinal fluid and the degree of cerebral vasospasm (P<.001). Pharmacological effects of nitrite infusion were also associated with the formation of S-nitrosothiol in cerebrospinal fluid. There was no clinical or pathological evidence of nitrite toxicity. Conclusion  Subacute sodium nitrite infusions prevented delayed cerebral vasospasm in a primate model of subarachnoid hemorrhage.      

The evolution of epidemiology and clinical characteristics of laryngeal and hypopharyngeal carcinoma in Poland from 1991 to 2001

On the base of retrospective analysis of 12,888 cases of carcinoma of larynx and hypopharynx, diagnosed in 19 ENT Departments in Poland from 1991 to 2001, the assessment of basic epidemiological data, including the localization of tumor and stage of local and clinical advancement of the disease at the time of diagnosis has been conducted. In analyzed period of 11 years the trends to change of the mentioned above parameters has been examined. The significant increase of female patients in this period was observed, with average proportion M:F = 8:1. The glottis localization of carcinoma dominated (47.6%), followed by supraglottis (40.8%) and pyriform fossa (7.8%), with significant increase of pyriform fossa tumors in the analyzed period of 11 years. In the majority of cases the carcinoma of larynx and hypopharynx was diagnosed in the advanced stage (T3 + T4) of local disease, with the highest percentage in localization within the pyriform fossa (81.0%), and the lowest percentage in glottis tumors (45.6%). The regional lymph nodes metastases has been diagnosed in 46.7% of the analyzed group, with the highest percentage in tumors localized in pyriform fossa (82.9%), and the lowest percentage in tumors of glottis localization (33.1%). In the 11 years time the significant drop down of N0 cases and tendency to increase of N2 and N3 in the supraglottis localization of tumor. The distant metastases in the analyzed group at the time of diagnosis has been registered in 2.0%, with the highest percentage in posterior pharyngeal wall (7.6%) and pyriform fossa (7.4%). The authors postulate the renewal of prospective study on epidemiology, clinical characteristics and treatment results of larynx and hypopharynx carcinoma in Poland.     

Some considerations about the procedure of informed consent in patients prepared for electroconvulsive treatment

Electroconvulsive therapy (ECT) as a medical procedure of higher risk as well as a therapy evoking certain controversies requires strict obedience to the conditions of acquiring the patient's informed consent to the offered method of treatment. To acquire the patient's consent it is necessary to inform him/her about the different aspects of electroconvulsive therapy. The paper stresses that in the case of ECT therapy, the spoken information given to the patient seems insufficient. It is necessary to work out a Polish questionnaire for acquiring the patient's consent to electroconvulsive therapy and to apply it in all psychiatric institutions that carry out ECT procedures.