A strychnine-sensitive site is involved in dynorphin-induced paralysis and loss of the tail-flick reflex

Dynorphin A(1-13) administered intrathecally to rats induces a reversible hindlimb paralysis and permanent loss of the tail-flick reflex in a dose-dependent and all-or-none manner. The loss of the tail-flick reflex has been determined to result from neurotoxicity linked to the N-methyl-D-aspartate (NMDA) receptor. Recently, it has been reported that NMDA antagonists attenuate irreversible paralysis induced by dynorphin A(1-17) and dynorphin A(2-17). In the present studies, we examined whether repeated injections of dynorphin A(1-13) acetate salt could change the characteristics of the reversible paralysis. Injections repeated every 48 h resulted in hindlimb paralysis upon each injection which was not different in terms of magnitude or duration (P greater than 0.60). Injections repeated at 2 h intervals resulted in desensitization of the paralytic effects (P less than 0.05). We also examined if strychnine sulfate, a glycine antagonist would alter the paralytic response to dynorphin. Strychnine protected rats from paralysis (P less than 0.01) and loss of the tail-flick reflex with an ED50 of 7 nmol. We conclude that the reversible paralysis induced by dynorphin A(1-13) is repeatable which suggests that the paralysis results from nontoxic or subtoxic actions of dynorphin. Desensitization to the paralytic effects occurs with closely spaced injections by some unknown mechanism. In addition, we conclude that the spinal glycinergic inhibitory system may participate in the induction of the paralysis because strychnine antagonizes dynorphin-induced paralysis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fecal microbiota transplantation and Clostridioides difficile infection among privately insured patients in the United States

Journal of Gastroenterology - Clostridioides difficile infection (CDI) may be rising in severity in the US over the past decade and its treatment landscape is changing given the recent adoption of...     

The effects of occipital ablation on a conditioned visual avoidance learning task in young and old rats

Previous data indicate that learning of a conditioned visual avoidance task following simultaneous complete bilateral occipital ablations is affected by the age of the organism as well as the postoperative recovery period. The present study investigated the performance of the avoidance task, following complete occipital ablations, in young and older rats given two different recovery intervals. Young rats given 10 days to recover performed more poorly than the young control animals; given 20 days to recover, young rats performed comparable to controls. Older rats given 10 days to recover performed significantly better than the controls; given 20 days to recover, older rats did not show a decrease in performance. The present finding is consistent with previous data which show that the occipital cortex exerted an inhibitory effect on the learning ability of the avoidance task in older rats, which, upon removal, enhanced the performance of these rats on the task.     

Delayed postburn blisters: an immunohistochemical and ultrastructural study

This study was performed in an attempt to further elucidate the pathogenesis of delayed postburn blistering. Two cases were studied ultrastructurally and immunohistochemically, 1 with blisters on the recipient site of autologous split-thickness skin grafts and the other on the donor site. Ultrastructurally, the basement membrane was on the roof of the blisters in both cases, except for a single small blister in the first case where it was on the dermal floor. In the blister roofs, the basement membrane showed small or marked segments of discontinuity. In the adjacent non-blistered healed skin, the basement membrane was usually continuous, and anchoring fibrils were present. Immunoperoxidase staining on frozen sections, using antibodies to laminin, laminin 5, collagen IV, and collagen VII, showed a mostly continuous linear pattern in the adjacent non-blistered skin, which often became discontinuous near the blisters and markedly discontinuous in the blister roofs. In the blister floors, weakly stained linear or granular deposits of some of these components were sometimes also present. The results of this study support discontinuity of the basement membrane as the main anomaly in delayed postburn blistering. Disturbance in die reassembly or local breakdown of the basement membrane components might be the underlying defect.     

Sexual changes in a case of gastric stapling in adolescence

This is the case of an adolescent female who developed a moderately severe depressive illness eighteen months after a gastric stapling procedure for morbid obesity. The weight loss following surgery was associated with an emergence of sexual awareness and interest, culminating in the patient's infatuation with a medical practitioner. The importance of an assessment of psychosexual development is discussed in relation to this procedure.     

Obesity and intermittent hypoxia increase tumor growth in a mouse model of sleep apnea

BackgroundIntermittent hypoxia and obesity which are two pathological conditions commonly found in patients with obstructive sleep apnea (OSA), potentially enhance cancer progression.ObjectiveTo investigate whether obesity and/or intermittent hypoxia (IH) mimicking OSA affect tumor growth.MethodsA subcutaneous melanoma was induced in 40 mice [22 obese (40–45 g) and 18 lean (20–25 g)] by injecting 10⁶ B16F10 cells in the flank. Nineteen mice (10 obese/9 lean) were subjected to IH (6 h/day for 17 days). A group of 21 mice (12 obese/9 lean) were kept under normoxia. At day 17, tumors were excised, weighed and processed to quantify necrosis and endothelial expression of vascular endothelial growth factor (VEGF) and CD-31. VEGF in plasma was also assessed.ResultsIn lean animals, IH enhanced tumor growth from 0.81 ± 0.17 to 1.95 ± 0.32 g. In obese animals, a similar increase in tumor growth (1.94 ± 0.18 g) was observed under normoxia, while adding IH had no further effect (1.69 ± 0.23 g). IH only promoted an increase in tumoral necrosis in lean animals. However, obesity under normoxic conditions increased necrosis, VEGF and CD-31 expression in tumoral tissue. Plasma VEGF strongly correlated with tumor weight (ρ = 0.76, p < 0.001) in the whole sample; it increased in lean IH-treated animals from 66.40 ± 3.47 to 108.37 ± 9.48 pg/mL, p < 0.001), while the high baseline value in obese mice (106.90 ± 4.32 pg/mL) was unaffected by IH.ConclusionsObesity and IH increased tumor growth, but did not appear to exert any synergistic effects. Circulating VEGF appeared as a crucial mediator of tumor growth in both situations.     

Reduced Bioavailability of Moisture-Exposed Carbamazepine Resulting in Status Epilepticus

A 28-year-old man with seizures well controlled with carbamazepine (CBZ) and valproate (VPA) developed generalized convulsive status epilepticus three days after his CBZ tablets became wet during a rainstorm while he was camping out. He continued the CBZ but avoided ingesting obviously disintegrating tablets. The VPA was not exposed to excessive moisture. Previous random CBZ blood levels had been in the range of 9–13 μg/ml; at the time of admission to the emergency room the level had decreased to 3.8 μg/ml. The VPA level did not change significantly from baseline. The moistureexposed CBZ tablets were of expected weight but were swollen and enlarged. Analysis of these tablets by USP paddle method 2 demonstrated a mean dissolution of 16% at 60 min as compared with >80% for fresh CBZ tablets. After final dissolution of the moisture-exposed CBZ tablets, normal quantities of active drug were noted. We propose that poor dissolution of moisture-exposed CBZ tablets results in reduced bioavailability. We urge caution in the packaging and storage of CBZ to avoid exposure to moisture.     

Neurodegeneration in the Central Nervous System of apoE-Deficient Mice

Apolipoprotein E (apoE) is involved in the development and regeneration of the central nervous system (CNS). ApoE may also be necessary to maintain the integrity of the synapto-dendritic complexity. We analyzed the synaptic alterations in the CNS of apoE-deficient (knockout) mice during the aging process. In apoE-deficient homozygous mice, there was an age-dependent 15 to 40% loss of synaptophysin-immunoreactive nerve terminals and microtubule-associated protein 2-immunoreactive dendrites in the neocortex and hippocampus, when compared to controls. Dendritic alterations were observed as early as 4 months of age. Ultrastructural analysis revealed extensive dendritic vacuolization and disruption of the endomembrane system and cytoskeleton in apoE-deficient homozygous mice. Further immunocytochemical studies of the neuronal cytoskeleton showed that in apoE-deficient mice there was a decrease in the immunoreactivity of α and β tubulin (but not kinesin) in the cell bodies and processes. These results support the contention that apoE might play an important role in maintaining the stability of the synapto-dendritic apparatus and that altered or deficient functioning of this molecule could underlie the synaptic and cytoskeletal alterations in Alzheimer's disease.     

Evaluation of tetracycline raw materials and finished products found on the Kenyan market

Contents of tetracycline, its degradation products (epitetracycline, epianhydrotetracycline, anhydrotetracycline) and a fermentation impurity (2-acetyl-2-decarboxamidotetracycline) were determined in four raw materials, 12 batches of six ointment products, four eye ointment products and nine batches of five capsule products, all sampled from the Kenyan market. The analytical method was liquid chromatography on a column packed with a poly(styrenedivinylbenzene) material (8-μm PLRP-S 100 Å). All raw materials and finished products had tetracycline contents and impurity levels within the prescribed compendial limits.