Class side effects: decreased pressure in the lower oesophageal and the pyloric sphincters after the administration of dopamine antagonists, neuroleptics, anti-emetics, L-NAME, pentadecapeptide BPC 157 and L-arginine.

The ulcerogenic potential of dopamine antagonists and L-NAME in rats provides unresolved issues of anti-emetic neuroleptic application in both patients and experimental studies. Therefore, in a 1-week study, we examined the pressures within the lower oesophageal and the pyloric sphincters in rats [assessed manometrically (cm H2O)] after dopamine neuroleptics/prokinetics, L-NAME, L-arginine and stable gastric pentadecapeptide BPC 157 were administered alone and/or in combination. Medication (/kg) was given once daily intraperitoneally throughout the 7 days, with the last dose at 24 h before pressure assessment. Given as individual agents to healthy rats, all dopamine antagonists (central [haloperidol (6.25 mg, 16 mg, 25 mg), fluphenazine (5 mg), levomepromazine (50 mg), chlorpromazine (10 mg), quetiapine (10 mg), olanzapine (5 mg), clozapine (100 mg), sulpiride (160 mg), metoclopramide (25 mg)) and peripheral(domperidone (10 mg)], L-NAME (5 mg) and L-arginine (100 mg) decreased the pressure within both sphincters. As a common effect, this decreased pressure was rescued, dose-dependently, by BPC 157 (10 µg, 10 ng) (also note that L-arginine and L-NAME given together antagonized each other's responses). With haloperidol, L-NAME worsened both the lower oesophageal and the pyloric sphincter pressure, while L-arginine ameliorated lower oesophageal sphincter but not pyloric sphincter pressure, and antagonized L-NAME effect. With domperidone, L-arginine originally had no effect, while L-NAME worsened pyloric sphincter pressure. This effect was opposed by L-arginine. All these effects were further reversed towards a stronger beneficial effect, close to normal pressure values, by the addition of BPC 157. In addition, NO level was determined in plasma, sphincters and brain tissue. Thiobarbituric acid reactive substances (TBARS) were also assessed. Haloperidol increased NO levels (in both sphincters, the plasma and brain), consistently producing increased TBARS levels in the plasma, sphincters and brain tissues. These effects were all counteracted by BPC 157 administration. In conclusion, we revealed that BPC 157 counteracts the anti-emetic neuroleptic class side effect of decreased pressure in sphincters and the dopamine/NO-system/BPC 157 relationship.

Hypermagnesemia disturbances in rats, NO-related: pentadecapeptide BPC 157 abrogates, L-NAME and L-arginine worsen.

AIM: Stable gastric pentadecapeptide BPC 157, administered before a high-dose magnesium injection in rats, might be a useful peptide therapy against magnesium toxicity and the magnesium-induced effect on cell depolarization. Moreover, this might be an NO-system-related effect. Previously, BPC 157 counteracts paralysis, arrhythmias and hyperkalaemia, extreme muscle weakness; parasympathetic and neuromuscular blockade; injured muscle healing and interacts with the NOS-blocker and NOS-substrate effects. MAIN METHODS: Assessment included magnesium sulfate (560 mg/kg intraperitoneally)-induced muscle weakness, muscle and brain lesions, hypermagnesemia, hyperkalaemia, increased serum enzyme values assessed in rats during and at the end of a 30-min period and medication (given intraperitoneally/kg at 15 min before magnesium) [BPC 157 (10 µg, 10 ng), L-NAME (5 mg), L-arginine (100 mg), alone and/or together]. In HEK293 cells, the increasing magnesium concentration from 1 to 5 mM could depolarize the cells at 1.75 ± 0.44 mV. KEY FINDINGS: L-NAME + magnesium-rats and L-arginine + magnesium-rats exhibited worsened severe muscle weakness and lesions, brain lesions, hypermagnesemia and serum enzymes values, with emerging hyperkalaemia. However, L-NAME + L-arginine + magnesium-rats exhibited all control values and normokalaemia. BPC 157 abrogated hypermagnesemia and counteracted all of the magnesium-induced disturbances (including those aggravated by L-NAME or L-arginine). Thus, cell depolarization due to increasing magnesium concentration was inhibited in the presence of BPC 157 (1 µM) in vitro. SIGNIFICANCE: BPC 157 likely counteracts the initial event leading to hypermagnesemia and the life-threatening actions after a magnesium overdose. In contrast, a worsened clinical course, higher hypermagnesemia, and emerging hyperkalaemia might cause both L-NAME and L-arginine to affect the same events adversely. These events were also opposed by BPC 157.

Association of age-related macular degeneration with erythrocyte antioxidant enzymes activity and serum total antioxidant status.

The aim was to estimate association of the oxidative stress with the occurrence of age-related macular degeneration (AMD). The activities of erythrocyte antioxidant enzymes: superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) and additionally serum total antioxidant status (TAS) were used as indicators of the oxidative stress level. 57 AMD patients (32 early and 25 late AMD) and 50 healthy, age and gender matched controls were included. GPx activity (P < 0.001) and serum TAS (P = 0.015) were significantly lower in AMD patients. The difference was not significant for SOD or CAT activities. Significant interaction between GPx and SOD was detected (P = 0.003). At high levels of SOD activity (over 75th percentile), one standard deviation decrease in GPx increases the odds for AMD for six times (OR = 6.22; P < 0.001). ROC analysis revealed that combined values of GPx activity and TAS are significant determinants of AMD status. Accuracy, sensitivity, specificity, and positive and negative predictive values were 75%, 95%, 52%, 69%, and 90%, respectively. The study showed that low GPx activity and TAS are associated with AMD. SOD modulates the association of GPx and AMD. The results suggest that erythrocyte antioxidant enzymes activity and serum TAS could be promising markers for the prediction of AMD.

Wartime open globe eye injuries.

BACKGROUND: Open globe injuries are the most serious eye injuries in war as in peace time. The purpose of this study is to analyze wartime open globe eye injuries in 72 patients treated at the Department of Ophthalmology, Clinical Hospital of Split from July 1991 to April 1993, during the intensive war in Croatia and Bosnia and Herzegovina, and to evaluate crucial factors responsible for the functional success of the treatment. METHODS: Wartime open globe eye injuries were retrospectively analyzed in 72 patients (80 eyes) hospitalized at Clinical Hospital of Split, Department of Ophthalmology, between July 1991 and April 1993. The causes and ways of wounding, localization of wounds and presence, nature and localization of the foreign body, as well as admission time, microsurgical management and other factors contributing to poor visual outcome were studied. Standard international classification of ocular traumas (the Birmingham Eye Trauma Terminology and the International Ocular Trauma Classification) was used for the classified and graded injuries. RESULTS: Open globe eye injuries amounted to 52.65% of all war injuries to the eyes. Bilateral injuries were found in eight patients (11.11%). The most frequent cause of the injures were fragments of explosive devices (more than two-thirds). Most of the patients were admitted to the hospital within 24 hours of the injury. Using current microsurgical techniques, the attempt was made to achieve not only anatomical but also functional recovery already in the primary treatment. In 30 eyes (37.50%) final visual acuity amounted to more than 0.1, and in 22 eyes (27.50%) it reached 0.5. There was a statistically significant correlation between admission within the first 12 hours and postoperative improved visual acuity (chi(2) = 4.53; p = 0.033). Statistically significantly better visual acuity was found in patients with lesions limited to the anterior segment of the eye. Primary enucleation or evisceration was performed only exceptionally: one enucleation and six eviscerations (8.75%). CONCLUSION: The most important factors in the prognosis of postoperational visual acuity for wartime open globe eye injuries were: (1) preoperative condition of the eye, (2) localization and extent of the wound, (3) presence, size and nature of foreign bodies, and (4) adequate surgical treatment in specialized institutions.