Neurotoxicity and oxidative stress induced by gibberellic acid in rats during late pregnancy and early postnatal periods: Biochemical and histological changes

Gibberellic acid (GA₃) is an endogenous plant growth regulator used worldwide in agriculture; however, little is known about its biochemical and physiological effects on mammals. This study investigated possible neurotoxic effects of GA₃ on the cerebrum and cerebellum of suckling rats. Female Wistar rats were given daily 200 ppm GA₃ in drinking water from the 14th day of pregnancy until day 14 after delivery. Acetylcholinesterase activity in both cerebellum and cerebrum was inhibited after treatment with GA₃. Neurotoxicity was demonstrated by a significant increase in malondialdehyde level and a decrease in the antioxidant enzyme activities of catalase, superoxide dismutase, glutathione peroxidase in the cerebrum and cerebellum of suckling pups. A significant decline of glutathione content and vitamin C was also observed. The biochemical parameters were correlated histologically with an abnormal development of the external granular layer and a loss of Purkinje cells in the cerebellum of GA₃-treated suckling rats.     

Oxidative stress induced by chromium (VI) in bone of suckling rats

Exposure to hexavalent chromium Cr(VI) compounds is of concern in many Cr-related industries and their surrounding environments. K(2)Cr(2)O(7) is widely recognized as an animal and human carcinogen, mutagen, and teratogen. The present study investigated the bone maturity of suckling rats whose mothers were treated with K(2)Cr(2)O(7). Experiments were carried out on female Wistar rats given 700 ppm of K(2)Cr(2)O(7) in their drinking water from the 14th day of pregnancy until day 14 after delivery. Exposing dams to K(2)Cr(2)O(7) caused disorders in the bone of their progeny. As corollary to this, malondialdehyde levels increased, while glutathione, a non-protein thiol and vitamin C decreased. Alteration of the antioxidant system in the treated group was also confirmed by the significant decline of superoxide dismutase, catalase, and glutathione peroxidase activities. Furthermore, K(2)Cr(2)O(7) induced changes in bone mineralization, especially calcium and phosphorus levels, which decreased. Whereas, in plasma and urine, they increased and decreased inversely. These results suggest that K(2)Cr(2)O(7) accelerated bone resorption activity. In fact, in treated pups, total tartrate-resistant acid phosphatase, which reflected bone resorption, was enhanced while total alkaline phosphatase, which reflected bone formation, was reduced. The impairment of bone function was corresponded histologically.     

Response of Arabidopsis thaliana, Seedlings to Cadmium in Relation to Ammonium Availability

This study explored the natural variability of Arabidopsis thaliana to find out its response to ammonium availability and characterize the tolerance capacity to cadmic stress under low, average or high nitrogen supplies. Growth was determined by different morphological traits and metabolic enzymes. Plant growth was inhibited by cadmium at low nitrogen regime. But, at average or high nitrogen conditions, plant growth seems to be no affected by cadmium. Cadmium inhibited glutamine synthetase activity and stimulated glutamate dehydrogenase one in order to tolerate cadmium stress. Cadmium enhanced proline and sugar tenor in average or high nitrogen plants parallel with activation of Rubisco. Observations show that cadmium-induced stress was alleviated by optimal ammonium availability.     

Gastric and colonic sarcoidosis. A case report

Sarcoidosis is a disseminated disease defined by the presence of non-caseous granulomas. Digestive localizations are rare and the stomach is the mostly affected. The diagnosis is frequently difficult. We report the case of a digestive (gastric and colic) and hepatic sarcoidosis in a 38-year old woman. The clinical and endoscopic findings initially suggested linitis plastica. Subsequently the discovery of gastric granulomas led to the diagnosis of sarcoidosis. Coloscopy and abdominal scan were performed discovering a colic, hepatic and splenic localizations which were asymptomatic.     

HLA class II polymorphism: Protective or risk factors to breast cancer in Tunisia?

HLA system plays a key role in the tumor cells’ escape from immune surveillance. Herein is the first report on the correlation of the susceptibility to breast cancer with HLA class II markers in Tunisia. Molecular typing of HLA-DRB1 and -DQB1 loci was undertaken for 70 Tunisian female patients. Comparison of allele and haplotype distribution between patients and 70 female control subjects reveals a negative association between HLA-DRB1*07-DQB1*02 and the incidence of breast cancer in the Tunisian population. (Pathology Oncology Research Vol 12, No 2, 79–81)     

Spinal Paget's disease with bilevel cord compression and ischemic non‐compressive myelopathy treated with zoledronic acid

Cord compression and ischemic non‐compressive myelopathy are a complication of spinal Paget''s disease (SPD). SPD usually touches a single spine level. We report an unusual case with bilevel spinal cord compression and dysfunction which was medically treated due to resolution of the vascular steal syndrome.     

Multiple mechanisms limit meiotic crossovers: TOP3α and two BLM homologs antagonize crossovers in parallel to FANCM

Meiotic crossovers (COs) have two important roles, shuffling genetic information and ensuring proper chromosome segregation. Despite their importance and a large excess of precursors (i.e., DNA double-strand breaks, DSBs), the number of COs is tightly regulated, typically one to three per chromosome pair. The mechanisms ensuring that most DSBs are repaired as non-COs and the evolutionary forces imposing this constraint are poorly understood. Here we identified Topoisomerase3α (TOP3α) and the RECQ4 helicases—the Arabidopsis slow growth suppressor 1 (Sgs1)/Bloom syndrome protein (BLM) homologs—as major barriers to meiotic CO formation. First, the characterization of a specific TOP3α mutant allele revealed that, in addition to its role in DNA repair, this topoisomerase antagonizes CO formation. Further, we found that RECQ4A and RECQ4B constitute the strongest meiotic anti-CO activity identified to date, their concomitant depletion leading to a sixfold increase in CO frequency. In both top3α and recq4ab mutants, DSB number is unaffected, and extra COs arise from a normally minor pathway. Finally, both TOP3α and RECQ4A/B act independently of the previously identified anti-CO Fanconi anemia of complementation group M (FANCM) helicase. This finding shows that several parallel pathways actively limit CO formation and suggests that the RECQA/B and FANCM helicases prevent COs by processing different substrates. Despite a ninefold increase in CO frequency, chromosome segregation was unaffected. This finding supports the idea that CO number is restricted not because of mechanical constraints but likely because of the long-term costs of recombination. Furthermore, this work demonstrates how manipulating a few genes holds great promise for increasing recombination frequency in plant-breeding programs.Meiotic homologous recombination is initiated by the formation of DNA double-strand breaks (DSBs). DSBs are resected to form 3′ ssDNA overhangs which invade the intact homologous chromosome, producing DNA joint molecules (JMs). These JMs can be differentially processed to produce crossovers (COs) or non-COs (NCOs). In Arabidopsis thaliana, mammals, and budding yeast, two pathways of CO formation exist. The major pathway depends on the ZMM proteins (for Zip1-4, Msh4/5, and Mer3) in addition to MutL homolog 1 (MLH1) and MuL homolog 3 (MLH3) and produces interfering COs, so that one CO prevents the formation of another nearby (1). The second, pathway, producing noninterfering COs, depends on structure-specific endonucleases including MUS81 (1). These pro-CO pathways compete with anti-CO pathways, resulting in a minor portion of DSBs becoming COs; for instance, it is estimated that COs represent only 10% and 5% of DSBs in mouse and in Arabidopsis, respectively (2). Three helicases with meiotic anti-CO activities have been identified in different species: the Bloom syndrome (BLM) homolog, small growth suppressor 1 (Sgs1) in Saccharomyces cerevisiae (3, 4); regulator of telomere elongation helicase1 (RTEL-1) in Caenorhabditis elegans (5), and the Fanconi anemia of complementation group M (FANCM) helicase in Arabidopsis and Schizosaccharomyces pombe (6, 7). These helicases are thought to displace the invading strand, allowing its annealing with the other 3′ overhang end of the DSB, leading to NCO formation in a process called “synthesis-dependent strand annealing” (SDSA). Nevertheless, even when CO formation is increased threefold by the disruption of AtFANCM, DSBs still greatly outnumber COs (6), suggesting the existence of additional anti-CO pathways.     

New Markers of Bone Fragility in Hemodialysis Patients: A Monocentric Study

Introduction: Mechanisms underlying bone fragility in patients under dialysis are various. The assessment of bone disorder is not yet codified in these patients. Our study aimed to determine the relationship between the serum fibroblast growth factor 23 (FGF23) level and bone fragility. We also aimed to assess the bone alkaline phosphatase (bAP) to the C-terminal telopeptide of type I (CTX) ratio and the FGF23*bAP product to CTX ratio in patients under hemodialysis. Methodology: We conducted a cross-sectional study, including 76 patients under hemodialysis. To assess bone fragility, we measured bAP, CTX, and FGF 23. We calculated the bAP to the CTX ratio (bAP/CTX) and the FGF23*bAP product to the CTX ratio (FGF23*bAP/CTX). We defined bone fragility as the existence of osteoporosis or fragility fractures. Receiver operating characteristic (ROC) curves were evaluated for each biological using the existence of osteoporosis or fragility fracture as the gold standard for bone fragility. Results: There were 51 men. The mean age was 53.36 ± 14.27 years. Bone fragility was noted in 25 cases. Patients with osteoporosis had higher FGF*bAP/CTX and bAP/CTX ratios. The ability of the ratio (bAP/CTX) to distinguish patients with osteoporosis from those without osteoporosis was good, with a ROC AUC of 0.707. The optimal ratio cut-off value with the highest accuracy was 9.72. The ability of the ratio (FGF23*bAP/CTX) to distinguish patients with bone fragility was good, with a ROC AUC of 0.701. The optimal ratio cut-off value with the highest accuracy was 1621.89 (sensitivity 60%, specificity 78.4%). Conclusion: Our study showed FGF23, FGF23*bAP product to CTX ratio, and the bAP to CTX ratio can be used as markers of bone fragility in hemodialysis patients. Therefore, these noninvasive and relatively inexpensive methods may serve to diagnose bone fragility in patients under hemodialysis.