Long-term Results of Splenectomy in Transfusion-dependent Thalassemia.

Splenectomy is indicated in transfusion-dependent thalassemia (TDT) only in certain situations. This study aimed to present the effectiveness, complications, and long-term follow-up results of splenectomy in children with TDT. We performed a 30-year single-institution analysis of cases of splenectomy for TDT between 1987 and 2017 and their follow-up until 2021. A total of 39 children (female/male: 24/15) were included. The mean age at splenectomy was 11.2±3.2 years, and their mean follow-up duration after splenectomy was 21.5±6.4 years. Response was defined according to the patient's annual transfusion requirement in the first year postsplenectomy and on the last follow-up year. Complete response was not seen in any of the cases; partial response was observed in 32.3% and no response in 67.6%. Thrombocytosis was seen in 87% of the patients. The platelet counts of 7 (17.9%) patients were >1000 (10 9 /L), and aspirin prophylaxis was given to 22 (56.4%) patients. Complications were thrombosis in 2 (5.1%) patients, infections in 11 (28.2%) patients, and pulmonary hypertension in 4 (10.2%) patients. Our study showed that after splenectomy, the need for transfusion only partially decreased in a small number of TDT patients. We think splenectomy can be delayed with appropriate chelation therapy up to higher annual transfusion requirement values.

The Efficacy of Oral Vitamin B12 Replacement for Nutritional Vitamin B12 Deficiency.

Standard treatment of vitamin B12 deficiency has not been well established in childhood, the ideal amount of supplemental vitamin B12 is not clear. Vitamin B12 deficiency is classically treated with intramuscular injections. In this study, we aimed to investigate the efficacy of oral therapy in children with vitamin B12 deficiency. Patients with serum cobalamin concentrations <300 pg/mL aged between 6 months to 18 years were included in this prospective study. Children were treated orally either with a combination of multivitamin tablet daily or vitamin B12 ampules. Serum specimens were obtained at the end of first and third months of treatment for vitamin B12 levels. A total of 79 patients were included in the study. The mean pretreatment vitamin B12 level increased from 182±47.6 pg/mL to 482±318 pg/mL after 1 month of treatment in the whole cohort. Comparison of the pretreatment vitamin B12 levels with first and third month posttreatment values showed significant difference (P-value, 0.001 and 0.028, respectively). In this study, oral cyanocobalamin was found effective for the treatment of vitamin B12 deficiency in children.

Utility of baseline serum phosphorus levels for predicting remission in acromegaly patients.

PURPOSE: High GH and IGF I levels increase tubular phosphate reabsorption in patients with acromegaly. We aimed to investigate the utility of serum phosphorus levels as an indicator for predicting chance of remission in acromegaly patients. DESIGN: Fifty-one patients (n: 51; F: 24, M: 27) with diagnosis of acromegaly were included in the study. Plasma IGF-1, Phosphorus (P) and nadir GH levels on oral glucose tolerance test (OGTT) at the time of diagnosis were analysed retrospectively. Patients were classified into two groups according to their plasma P levels; P ≤ 4.5 mg/dl (Group-1, n: 23, 45.1%), P > 4.5 mg/dl (Group-2, n: 28, 54.9%). Two groups were compared according to remission status; remission (n: 27) and non-remission (n: 24). Remission was defined with absence of clinical symptoms, normal plasma IGF-1 (adjusted for age and gender) and GH levels (<1 mcg/dl) at least 3 months after initial treatment. RESULTS: Serum P levels decreased significantly after treatment in both groups (p < 0.001). There was a significant correlation between baseline phosphorus levels and remission rates, nadir GH in OGTT, pituitary adenoma size and Ki-67 scores (p = 0.001, r: -0.51; p = 0.01, r: 0.44; p = 0.001, r: 0.52; p = 0.02, r: 0.71, respectively). Mean baseline P levels were significantly higher in patients with non-remission (4.8 vs 4.2, P < 0.001). Logistic regression analysis did not reveal an independent effect on remission with any of these risk factors. CONCLUSION: High serum P levels may be an indicator for a low likelihood of onset of remission in acromegaly patients. Further studies with wider spectrum are needed to make specific suggestions.

Molecular hydrogen in drinking water protects against neurodegenerative changes induced by traumatic brain injury.

Traumatic brain injury (TBI) in its various forms has emerged as a major problem for modern society. Acute TBI can transform into a chronic condition and be a risk factor for neurodegenerative diseases such as Alzheimer's and Parkinson's diseases, probably through induction of oxidative stress and neuroinflammation. Here, we examined the ability of the antioxidant molecular hydrogen given in drinking water (molecular hydrogen water; mHW) to alter the acute changes induced by controlled cortical impact (CCI), a commonly used experimental model of TBI. We found that mHW reversed CCI-induced edema by about half, completely blocked pathological tau expression, accentuated an early increase seen in several cytokines but attenuated that increase by day 7, reversed changes seen in the protein levels of aquaporin-4, HIF-1, MMP-2, and MMP-9, but not for amyloid beta peptide 1-40 or 1-42. Treatment with mHW also reversed the increase seen 4 h after CCI in gene expression related to oxidation/carbohydrate metabolism, cytokine release, leukocyte or cell migration, cytokine transport, ATP and nucleotide binding. Finally, we found that mHW preserved or increased ATP levels and propose a new mechanism for mHW, that of ATP production through the Jagendorf reaction. These results show that molecular hydrogen given in drinking water reverses many of the sequelae of CCI and suggests that it could be an easily administered, highly effective treatment for TBI.

Targeted mutagenesis of mitochondrial carbonic anhydrases VA and VB implicates both enzymes in ammonia detoxification and glucose metabolism.

Prior studies with carbonic anhydrase (CA) inhibitors implicated mitochondrial CA in ureagenesis and gluconeogenesis. Subsequent studies identified two mitochondrial CAs. To distinguish the contribution of each enzyme, we studied the effects of targeted disruption of the murine CA genes, called Car5A and Car5B. The Car5A mutation had several deleterious consequences. Car5A null mice were smaller than wild-type littermates and bred poorly. However, on sodium-potassium citrate-supplemented water, they produced offspring in expected numbers. Their blood ammonia concentrations were markedly elevated, but their fasting blood sugars were normal. By contrast, Car5B null mice showed normal growth and normal blood ammonia levels. They too had normal fasting blood sugars. Car5A/B double-knockout (DKO) mice showed additional abnormalities. Impaired growth was more severe than for Car5A null mice. Hyperammonemia was even greater as well. Although fertile, DKO animals were produced in less-than-predicted numbers even when supplemented with sodium-potassium citrate in their drinking water. Survival after weaning was also reduced, especially for males. In addition, fasting blood glucose levels for DKO mice were significantly lower than for controls (153 ± 33 vs. 230 ± 24 mg/dL). The enhanced hyperammonemia and lower fasting blood sugar, which are both seen in the DKO mice, indicate that both Car5A and Car5B contribute to both ammonia detoxification (ureagenesis) and regulation of fasting blood sugar (gluconeogenesis). Car5A, which is expressed mainly in liver, clearly has the predominant role in ammonia detoxification. The contribution of Car5B to ureagenesis and gluconeogenesis was evident only on a Car5A null background.

Carbon tetrachloride-induced nephrotoxicity in rats: protective role of Digera muricata.

Digera muricata is used in renal disorders in folk medicine. Generation of reactive radicals has been implicated in carbon tetrachloride-induced nephrotoxicity, which are involved in lipid peroxidation, accumulation of dysfunctional proteins, leading to injuries in kidneys. The present study was aimed to evaluate the efficacy of Digera muricata on the kidney function in CCl(4)-induced injuries. CCl(4) treatment (5 ml/kg body wt., i.p. CCl(4):olive oil; 1:9) significantly increased the level of urine creatinine, protein, nitrite, urobilinogen, red blood cells (RBCs), leucocytes count, and levels of blood urea nitrogen (BUN). Level of proteins and DNA fragmentation %, argyrophilic nucleolar organizer regions (AgNORs) count in renal tissues was also significantly increased. Activity of antioxidant enzymes; catalase, peroxidase, superoxide dismutase and reduced glutathione (GSH) were decreased while thiobarbituric acid reactive substances (TBARSs) were increased with CCl(4) treatment. DNA ladder assay was intimately related with the DNA fragmentation assay. Telomerase activity was determined in the CCl(4)-treated renal tissue homogenate. Treatment with n-hexane (HDMP) and methanolic (MDMP) extracts of Digera muricata (200 and 250 mg/kg body wt., oral, respectively) effectively attenuated the alterations in the biochemical markers, telomerase activity was inhibited and confirms the restoration of normalcy and accredits the protective role of Digera muricata against CCl(4)-induced nephrotoxicity.

Expression, assay, and structure of the extracellular domain of murine carbonic anhydrase XIV: implications for selective inhibition of membrane-associated isozymes.

Carbonic anhydrase (CA) XIV is the most recently identified mammalian carbonic anhydrase isozyme, and its presence has been demonstrated in a number of tissues. Full-length CA XIV is a transmembrane protein composed of an extracellular catalytic domain, a single transmembrane helix, and a short intracellular polypeptide segment. The amino acid sequence identity of human CA XIV relative to the other membrane-associated isozymes (CA IV, CA IX, and CA XII) is 34-46%. We report here the expression and purification of both the full-length enzyme and a truncated, secretory form of murine CA XIV. Both forms of this isozyme are highly active, and both show an abrogation of activity in the presence of 0.2% SDS, in contrast to the behavior of murine CA IV. We also report the crystal structure of the extracellular domain of murine CA XIV at 2.8 A resolution and of an enzyme-acetazolamide complex at 2.9 A resolution. The structure shows a monomeric glycoprotein with a topology similar to that of other mammalian CA isozymes. Based on the x-ray crystallographic results, we compare and contrast known structures of membrane-associated CA isozymes to rationalize the structural elements responsible for the SDS resistance of CA IV and to discuss prospects for the design of selective inhibitors of membrane-associated CA isozymes.