Neurotoxic effects of pregabalin dependence on the brain frontal cortex in adult male albino rats.

Pregabalin (PGB) is an analog of the inhibitory neurotransmitter gamma-aminobutyric acid. The currently available evidence favors the misuse and abuse potential of PGB. However, its neurotoxicity remains unclear. Therefore, this study assessed the toxic effects of chronic pregabalin dependence as well as withdrawal on the cortical neurons of the frontal lobe. This study included eighty adult male albino rats which were divided into three groups. Group I (Control) included 40 rats and was further subdivided into two equal subgroups (IA and IB) as negative and positive controls. Group II (PGB-dependent) included 20 rats which received PGB starting with the therapeutic dose (300 mg/day), then the doses were gradually increased until they reached the dependent dose (3400 mg/day) by the end of the first month. Further, the dependent dose was given daily for another 2 months. Group III (PGB withdrawal) included 20 rats which received PGB as described in group II. After that, administration of PGB was stopped and the rats were kept for another one month. By the end of the experiment, all animals were sacrificed by cervical decapitation. The specimens were taken from the frontal cortex for histologic and immunohistochemical staining as well as morphometric analysis. Sections of the frontal cortex of group II showed changes in the form of disturbed architectural pattern of cortical layers, apoptotic cells, weak immunoexpression of Bcl-2 and VEGF as well as moderate-strong immunoexpression of iNOS and nestin. These expressions were significantly different from the control groups, but they were non-significant in comparison with group III. These findings indicate that chronic PGB dependence induces neurotoxic effects mainly in the form of neuronal apoptosis, gliosis, and oxidative stress injury of the frontal cortex. The PGB- induced neurotoxic effects persisted after withdrawal. The influence of these neurotoxic effects and their relevance to the cognitive or neurologic disorders in PGB-dependent individuals warrants further research. Furthermore, it is recommended to quantify the behavioral changes related to PGB dependence as well as withdrawal in future studies.

S-100ß in predicting the need of hyperbaric oxygen in CO-induced delayed neurological sequels.

BACKGROUND: Delayed neurological sequels (DNS) have been described after carbon monoxide (CO) poisoning. There is a need to find a new prognostic marker to guide the use of hyperbaric oxygen (HBO) therapy. AIM: To evaluate serum S-100ß level in patients presenting with acute CO poisoning as an indicator of poisoning severity and predictor of DNS occurrence and HBO need in those patients. METHODS: This prospective cohort study included patients with acute CO poisoning. On admission, carboxyhemoglobin (COHb) and S-100ß levels were measured. Patients were followed up for 6 months for signs of DNS. RESULTS: Out of 50 patients, 6 only developed DNS. The mean of S-100ß levels was significantly higher in patients with severe poisoning and those with DNS. Receiver operating characteristic curve analysis revealed that S-100ß had an area under the curve 0. 871; at a cutoff value ≥ 0.67 µg/L, its sensitivity and specificity were 100% and 77.3%, respectively. The sensitivity of S-100ß was significantly higher than that of COHb, while its specificity and overall accuracy were significantly higher than those of HBO criteria. CONCLUSION: Serum S-100ß level on admission could be a marker of poisoning severity and a predictor of CO-induced DNS development that guides the use of HBO therapy.

Comparison of different scores as predictors of mechanical ventilation in drug overdose patients.

The decision of intubation and mechanical ventilation in poisoned patients with impaired consciousness can be a difficult task. The present study aimed to evaluate the power of Glasgow Coma Scale (GCS), acute physiology and chronic health evaluation (APACHE II), rapid acute physiology score (RAPS) and rapid emergency medicine score (REMS) at admission in predicting the need of intubation and mechanical ventilation in drug overdose patients with disturbed consciousness level (DCL). This prospective observational study was conducted on 104 poisoned patients who were admitted to Tanta Toxicological Unit with a DCL. Four scoring systems (GCS, APACHE II, RAPS and REMS) were recorded for all patients on admission. Discrimination was evaluated using receiver operating characteristics curve and calculating the area under the curve (AUC). Twenty-four cases required mechanical ventilation. The mechanically ventilated patients had significantly lower value of GCS and higher values of APACHE II, REMS and RAPS than other group ( p < 0.001). Although the APACHE II score has the best AUC value (0.796) in predicting mechanical ventilation, there was no statistically significant difference between the four scores. GCS > 8 had 100% negative predictive value, while REMS > 8 had 100% positive predictive value.