An update review of post-transplant diabetes mellitus: Concept, risk factors, clinical implications and management.

OBJECTIVE: Kidney transplantation is the gold standard therapeutic alternative for patients with end-stage renal disease; nevertheless, it is not without potential complications leading to considerable morbidity and mortality such as post-transplant diabetes mellitus (PTDM). This narrative review aims to comprehensively evaluate PTDM in terms of its diagnostic approach, underlying pathophysiological pathways, epidemiological data, and management strategies. METHODS: Articles were retrieved from electronic databases using predefined search terms. Inclusion criteria encompassed studies investigating PTDM diagnosis, pathophysiology, epidemiology, and management strategies. RESULTS: PTDM emerges as a significant complication following kidney transplantation, influenced by various pathophysiological factors including peripheral insulin resistance, immunosuppressive medications, infections, and proinflammatory pathways. Despite discrepancies in prevalence estimates, PTDM poses substantial challenges to transplant. Diagnostic approaches, including traditional criteria such as fasting plasma glucose (FPG) and HbA1c, are limited in their ability to capture early PTDM manifestations. Oral glucose tolerance test (OGTT) emerges as a valuable tool, particularly in the early post-transplant period. Management strategies for PTDM remain unclear, within sufficient evidence from large-scale randomized clinical trials to guide optimal interventions. Nevertheless, glucose-lowering agents and life style modifications constitute primary modalities for managing hyperglycemia in transplant recipients. DISCUSSION: The complex interplay between PTDM and the transplant process necessitates individualized diagnostic and management approaches. While early recognition and intervention are paramount, modifications to maintenance immunosuppressive regimens based solely on PTDM risk are not warranted, given the potential adverse consequences such as increased rejection risk. Further research is essential to refine management strategies and enhance outcomes for transplant recipients.

The effects of dexmedetomidine on early acute kidney injury in severely burned rats.

OBJECTIVE: Burns are a global medical and economic problem. In addition to high costs, the lengthy therapeutic process and the emotional trauma experienced by patients and their families indirectly worsen the socioeconomic damage caused. Kidney failure observed after burns is highly correlated with mortality. MATERIALS AND METHODS: Twenty-eight male Sprague-Dawley rats (age four months, weight 250-350 g) were included in the study. They were randomly assigned into four groups consisting of seven rats each with similar mean weights. Group 1 (n=7) represented the healthy control group (C), Group 2 (n=7) the Sham+dexmedetomidine (DEX) 100 mcg/kg (three doses) (S+DEX100) group, Group 3 (n=7) the 30% Burn (B), and Group 4 (n=7) the 30% Burn+DEX 100 mcg/kg/day group (B+DEX100) (three doses). Thiobarbituric acid reactive substances (TBARS), total thiol (TT), interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) values in kidney tissues were investigated biochemically, and histopathological analyses were also performed. Nuclear factor κB (NF-κB)/p65 was measured using immunohistochemistry, and the TUNEL assay was applied to indicate apoptotic tubular epithelial cells. RESULTS: TBARS, IL-1, and TNF-α in kidney tissues decreased in the B+DEX100 group compared to the 30% burn group, while total thiol values increased. Histopathologically, atypical glomeruli, particularly necrotic tubules, and inflammation in peritubular areas decreased in the B+DEX100 group compared to the 30% burn group. In addition, apoptotic tubular epithelial cells exhibiting TUNEL positivity and tubular epithelial cells exhibiting NF-кß/p65 positivity also decreased in the B+DEX100 group compared to the 30% burn group. CONCLUSIONS: Dexmedetomidine reduced apoptotic activity in rats and exhibited anti-inflammatory antioxidant effects in the burn model in this study.

An assessment of the relation between vitamin D levels and electroencephalogram (EEG) changes in migraine patients.

BACKGROUND: The present study evaluated vitamin D therapy in migraine patients with vitamin D deficiency and EEG abnormality. METHODS: 140 patients were divided into four groups: Group A; normal vitamin D and EEG, Group B; low vitamin D and normal EEG, Group C; normal vitamin D and pathological EEG, and Group D; low vitamin D and pathological EEG. Patients with low vitamin D received vitamin D therapy. RESULTS: Paediatric Migraine Disability Assessment Scale (PedMIDAS) scores and median attack frequencies time-dependent changes in the patients receiving vitamin D therapy in Group B were significant (p 0.05). Interictal EEG was pathological in 41 (29.3 %) patients. The main EEG findings were focal/hemispheric spike/sharp wave activity at 9.3 %, bilateral/generalized spike/sharp wave activity at 8.6 %, focal slowing at 5.8 %, and bilateral slow-wave activity/background rhythm irregularity at 3.6 %. Changes in EEG findings in between the groups C and D were not significant (p >0.05). There was no significant association between vitamin D levels 0.05). CONCLUSION: Vitamin D therapy positively affects attack frequency and PedMIDAS scores in migraine patients with vitamin D deficiency/insufficiency. No association was determined between EEG findings and vitamin D levels or therapy (Tab. 6, Ref. 35).

The nephroprotective effect of amifostine in a cecal ligation-induced sepsis model in terms of oxidative stress and inflammation.

OBJECTIVE: Sepsis is responsible for more than 5 million deaths worldwide every year. The purpose of this study was to use amifostine to reduce acute kidney injury developing as a result of sepsis. MATERIALS AND METHODS: Thirty Sprague Dawley rats were divided into three equal groups - a healthy control group (Group 1), cecal ligation and puncture group (CLP, Group 2), and a CLP + amifostine (AMF) group receiving a total of 200 mg/kg AMF intraperitoneally (i.p.) 15 min before sepsis induction (Group 3). RESULTS: Total thiol levels decreased while malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB/p65), and interleukin (IL)-1ß, and IL-6 levels increased in the CLP group. We also observed degeneration in renal corpuscles, necrotic tubules, polymorphonuclear leukocyte inflammation, and vascular congestion. In the amifostine group, total thiol levels in tissue increased, while MDA, TNF-α, NF-кB/p65, IL-1ß, and IL-6 levels, necrotic renal tubules, and inflammation decreased. CONCLUSIONS: Amifostine prevented sepsis-related acute kidney injury by reducing inflammation and oxidative stress.

Effects of oral zinc administration on long-term ipsilateral and contralateral testes damage after experimental testis ischaemia-reperfusion.

The purpose of this study was to examine potential long-term post-torsion changes that can occur in the histopathology, biochemistry and spermatogenesis of both torsioned and nontorsioned opposite testes. The study also determines the effect of zinc (Zn) administration on the testicular torsion/detorsion (T/D) damage on both testes. Forty-eight male rats, divided equally into eight groups: (SHAM), (SHAM+,Zn+), (T/D+, Zn- 1 month), (T/D+,Zn- 2 months), (T/D+,Zn- 3 months), (T/D+,Zn+ 1 months), (T/D+,Zn+ 2 months), (T/D+,Zn+ 3 months), have been used. Drug administration was carried out by adding 100 µg (0.016 ml/rat) Zn per rat to drinking water in related groups. Testicular damage decreased superoxide dismutase (SOD) and glutathione (GSH) and increased malondialdehyde (MDA) in the testis tissues of rats, while Zn administration increased SOD and GSH and decreased MDA in the testis tissues in comparison with the SHAM group. The beneficial effect of zinc sulphate was more evident on the nonrotated testis than the rotated testis. In the histopathological study, a significant decrease in torsion and detorsion injuries was observed in the treatment groups compared to the torsion and detorsion groups. We found a protective effect of zinc sulphate on oxidative stress as a result of T/D injuries in rats, especially for the nonrotated testis; results were supported histopathologically.

Is there any correlation between levels of serum ostepontin, CEA, and FDG uptake in lung cancer patients with bone metastasis? / ¿Existe correlación entre los niveles de osteopontina en suero sanguíneo, CEA y captación de 18F-FDG en pacientes con metástasis óseas por cáncer de pulmón?

Objective. In this study, an evaluation was made of the relationship between the serum levels of carcinoembryonic antigen (CEA), osteopontin (OPN), and the semi-quantitative parameters of 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in lung cancer patients with bone metastasis. Material and methods. The evaluation included 42 non-small cell lung cancer (NSCLC) and 31 small cell lung cancer (SCLC) patients who were referred to our institution for staging by 18F-FDG PET/CT. The biochemical parameters measured included CEA and OPN serum levels. Results. Serum levels of OPN in NSCLC patients with and without bone metastasis were 21.20 ± 4.97 ng/ml and 13.33 ± 4.53 ng/ml, respectively (p < 0.05). In SCLC patients with and without bone metastasis serum OPN levels were 23.95 ± 4.78 ng/ml and 17.30 ± 3.09 ng/ml, respectively (p < 0.05). Serum levels of CEA in NSCLC patients with and without bone metastasis were 33.79 ± 6.49 ng/ml and 11.74 ± 2.96 ng/ml, respectively (p < 0.05). In SCLC patients with and without bone metastasis serum levels of CEA were 28.93 ± 4.59 ng/ml and 13.88 ± 4.47 ng/ml, respectively (p < 0.05). There were no correlations between primary tumor SUVmax, and serum levels of CEA and OPN. Conclusions. Bone metastasis can be detected in patients with lung cancer by measuring CEA and OPN levels. Increased levels of CEA and OPN levels may be considered an early warning sign in patients needing accurate imaging, as they are at higher risk of bone metastasis (AU)

Objetivo. Evaluar la relación entre los niveles de antígeno carcinoembriionario (CEA), osteopontina (OPN) y los valores semicuantitativos (SUV) de la PET/TC con 18F-FDG en pacientes con metástasis óseas por cáncer de pulmón. Material y método. Se incluyeron 40 pacientes con cáncer de pulmón de células no pequeñas (NSCLC) y 31 pacientes con cáncer de pulmón de células pequeñas (SCLC) referidos a nuestro centro para la realización de un estudio PET/TC con 18F-FDG de estadificación. Se analizarón los niveles sanguíneos de OPN y CEA. Resultados. Los niveles de OPN en pacientes con NSCLC con y sin metástasis óseas fueron de 21.20 ± 4.97 ng/ml y 13.33 ± 4.53 ng/ml, respectivamente (p < 0.05). En pacientes con SCLC con y sin metástasis óseas fueron de 23.95 ± 4.78 ng/ml y 17.30 ± 3.09 ng/ml, respectivamente (p < 0.05). Los niveles sanguíneos de CEA en pacientes de NSCLC con y sin metástasis óseas fueron de 33.79 ± 6.49 ng/ml y 11.74 ± 2.96 ng/ml, respectivamente (p < 0.05). En pacientes con SCLC con y sin metástasis óseas fueron de 28.93 ± 4.59 ng/ml y 13.88 ± 4.47 ng/ml, respectivamente (p < 0.05). No hubo correlación entre el SUV máximo del tumor primario, los niveles OPN ni de CEA. Conclusiones. La metástasis ósea puede ser detectada en pacientes con cáncer de pulmón con la determinación de los niveles de OPN y CEA. Los niveles incrementados de CEA y OPN pueden ser considerados como una señal de advertencia temprana en pacientes que necesiten imágenes precisas, porque ellos están en mayor riesgo de metástasis en el hueso (AU)

Is there any correlation between levels of serum ostepontin, CEA, and FDG uptake in lung cancer patients with bone metastasis?

OBJECTIVE: In this study, an evaluation was made of the relationship between the serum levels of carcinoembryonic antigen (CEA), osteopontin (OPN), and the semi-quantitative parameters of 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) in lung cancer patients with bone metastasis. MATERIAL AND METHODS: The evaluation included 42 non-small cell lung cancer (NSCLC) and 31 small cell lung cancer (SCLC) patients who were referred to our institution for staging by (18)F-FDG PET/CT. The biochemical parameters measured included CEA and OPN serum levels. RESULTS: Serum levels of OPN in NSCLC patients with and without bone metastasis were 21.20±4.97 ng/ml and 13.33±4.53 ng/ml, respectively (p<0.05). In SCLC patients with and without bone metastasis serum OPN levels were 23.95±4.78 ng/ml and 17.30±3.09 ng/ml, respectively (p<0.05). Serum levels of CEA in NSCLC patients with and without bone metastasis were 33.79±6.49 ng/ml and 11.74±2.96 ng/ml, respectively (p<0.05). In SCLC patients with and without bone metastasis serum levels of CEA were 28.93±4.59 ng/ml and 13.88±4.47 ng/ml, respectively (p<0.05). There were no correlations between primary tumor SUVmax, and serum levels of CEA and OPN. CONCLUSIONS: Bone metastasis can be detected in patients with lung cancer by measuring CEA and OPN levels. Increased levels of CEA and OPN levels may be considered an early warning sign in patients needing accurate imaging, as they are at higher risk of bone metastasis.

Effects of amlodipine on ischaemia/reperfusion injury in the rat testis.

The aim of this study was to examine the effects of amlodipine (AML) in rat testicular torsion/detorsion damage. In this study, rats were divided into eight groups: (i) sham; (ii) testicular ischaemia, 2 h of ischaemia; (iii) testicular ischaemia/reperfusion (I/R), 2 h of ischaemia followed by 2 h of reperfusion; (iv) ischaemia + AML (5 mg kg(-1)) administered 30 min before ischaemia; (v) ischaemia + AML (10 mg kg(-1)) administered 30 min before ischaemia; (vi) and (vii) I/R + AML (5 mg kg(-1)) and I/R + AML (10 mg kg(-1)) administered 1.5 h after the induction of ischaemia, respectively, and at the end of a 2-h ischaemia period and a 2-h reperfusion period applied; and (viii) sham + AML (10 mg kg(-1)). Significant decreases in levels of superoxide dismutase and glutathione were observed in ischaemia and reperfusion groups when compared with healthy controls. These antioxidant levels increased in AML groups while malondialdehyde levels significantly decreased. While increases in tumour necrosis factor-alpha and transforming growth factor-beta levels were found in the torsion and detorsion groups, significant decreases in the levels of these inflammatory cytokines were observed in the treatment groups. These results demonstrate that AML significantly produced protective effects on testis tissue damage that occurs in the torsion/detorsion model via biochemical, histopathological and molecular pathways.

Agomelatine: an antidepressant with new potent hepatoprotective effects on paracetamol-induced liver damage in rats.

Paracetamol was shown to induce hepatotoxicity or more severe fatal acute hepatic damage. Agomelatine, commonly known as melatonin receptor agonist, is a new antidepressant, which resynchronizes circadian rhythms with subjective and objective improvements in sleep quality and architecture, as melatonin does. In the present study, it was aimed to evaluate the hepatoprotective activity of agomelatine on paracetamol-induced hepatotoxicity and to understand the relationship between the hepatoprotective mechanism of agomelatine and antioxidant system and proinflammatory cytokines. A total of 42 rats were divided into 7 groups as each composed of 6 rats: (1) intact, (2) 40 mg/kg agomelatine, (3) 140 mg/kg N-acetylcysteine (NAC), (4) 2 g/kg paracetamol, (5) 2 g/kg paracetamol + 140 mg/kg NAC, (6) 2 g/kg paracetamol + 20 mg/kg agomelatine, and (7) 2 g/kg paracetamol + 40 mg/kg agomelatine groups. Paracetamol-induced hepatotoxicity was applied and liver and blood samples were analyzed histopathologically and biochemically. There were statistically significant increases in the activities of aspartate aminotransferase, alanine aminotransferase, levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) and 8-iso-prostane, and decreases in the activity of superoxide dismutase and level of glutathione in the group treated with paracetamol. Administration of agomelatine and NAC separately reversed these changes significantly. In conclusion, agomelatine administration protects liver cells from paracetamol-induced hepatotoxicity via antioxidant activity and reduced proinflammatory cytokines, such as TNF-α and IL-6.

Removal of cadmium and lead from aqueous solution by Enterococcus faecium strains.

Foods may be contaminated with heavy metals, which, even in small quantities, possess detrimental effects on human health. The aim of the present study was to investigate the uptake of cadmium or lead from an aqueous medium frequently found in foods, by 2 Enterococcus faecium strains (E. faecium EF031 and E. faecium M74). Also, the effects of the bacterial viability, incubation (contact) time, and pH on the binding capacities and binding stability were assessed. The results showed that both of the strains efficiently removed cadmium and lead. While EF031 removed 77.3% to 98.1% of cadmium and 66.9% to 98.9% of lead, M74 removed 53.5% to 91% of cadmium and 42.9% to 93.1% of lead throughout a 48 h incubation period at pH 5. It was found that, at 1 h, EF031 and M74 strains removed cadmium and lead, which was more than 60% of total removed cadmium and lead throughout the whole incubation period of 48 h. It suggests that the uptake of cadmium and lead by EF031 and M74 strains is a rapid process. The binding of both heavy metals increased with increasing pH of an aqueous medium and was the highest at pH 5. Also, the complexes formed between both heavy metals and bacterial cells were found to be stable. These findings indicate that E. faecium strains used in the study are able to bind the 2 heavy metals and may be used in the production of fermented functional foods, which will be healthy via its detoxification properties.

Measurement of the oxidation-reduction potential of cheddar cheese.

The objective of this study was to develop a method to measure the oxidation-reduction (redox) potential of hard cheeses such as cheddar and to investigate the impact on this parameter of measurement temperature, and factors associated with electrochemical cell design such as distance between reference and working electrodes and depth into the cheese of the platinum electrodes. For this purpose, a novel, self-sealing, platinum working electrode was constructed which was thin and flexible enough to be inserted directly into the cheese sample. A calomel electrode was used as the reference electrode and the circuit was completed with a 3 M KCl salt bridge. The physical orientation of electrodes, such as distance between reference electrode and working electrode, had a substantial effect on equilibrium time for redox potential measurement. The time required for redox potential to reach equilibrium was 2 d in cheddar cheese and the optimum distance between the platinum and calomel electrodes was 2.5 cm. The fastest equilibration time was obtained when the working electrode was inserted 5 or 6 cm into the cheese. Temperature also had an important effect on redox potential. The shortest time to reach equilibrium of potential was at room temperature (20 degrees C), but it was not practical to keep cheese at this temperature for a period of 2 d. Therefore, redox measurement at 12 degrees C was recommended in spite of the longer equilibration time compared with room temperature. The results of this study suggest that the novel platinum working electrode allows reproducible measurement of the oxidation-reduction potential of cheddar cheese.

Short-term melatonin treatment improved diabetic nephropathy but did not affect hemorheological changes in diabetic rats.

Increased oxidative stress and hemorheological disturbances may play very important roles in the development of microangiopathies in diabetes mellitus. This study was designed to determine the healing effect of melatonin on hemorheological parameters and diabetic nephropathy in streptozotocin (STZ)-induced diabetic rats. Wistar male rats were divided into four groups as control, untreated-diabetic, melatonin-treated control and melatonin-treated diabetic rats. Diabetes was induced by injecting streptozotocin (45 mg/kg, i.p.). Fourteen weeks after inducement of diabetes, melatonin (10 mg/kg) was administered intraperitoneally for 5 days to the rats. Erythrocyte deformability and aggregation were measured by laser differaction analysis (LORCA). Diabetic nephropathy was assessed by histopathologic evaluation and TUNEL stain in the diabetic kidney. Decreased erythrocyte deformability and increased erythrocyte aggregation indices were determined in the diabetic group. Melatonin treatment did not improve these hemorheological abnormalities. However, renal injuries were diminished in the melatonin-treated diabetic group compared to the untreated diabetic group. Also, melatonin had an antiapoptotic effect on the diabetic kidney. It was concluded that i.p. administration of melatonin for 5 days improved renal injury in diabetic rats, probably by decreasing oxidative stress, but did not affect hemorheological changes.

Effect of melatonin on brain oxidative damage induced by traumatic brain injury in immature rats.

Progressive compromise of antioxidant defenses and free radical-mediated lipid peroxidation, which is one of the major mechanisms of secondary traumatic brain injury (TBI), has also been reported in pediatric head trauma. In the present study, we aimed to demonstrate the effect of melatonin, which is a potent free radical scavenger, on brain oxidative damage in 7-day-old rat pups subjected to contusion injury. Whereas TBI significantly increased thiobarbituric acid reactive substances (TBARS) levels, there was no compensatory increase in the antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx) 24 hours after TBI in 7-day-old rats. Melatonin administered as a single dose of 5 mg/kg prevented the increase in TBARS levels in both non-traumatized and traumatized brain hemispheres. In conclusion, melatonin protects against oxidative damage induced by TBI in the immature brain.

Effects of melatonin on oxidative stress and spatial memory impairment induced by acute ethanol treatment in rats.

Melatonin has recently been suggested as an antioxidant that may protect neurons from oxidative stress. Acute ethanol administration produces both lipid peroxidation as an indicator of oxidative stress in the brain and impairs water-maze performance in spatial learning and memory tasks. The present study investigated the effect of melatonin against ethanol-induced oxidative stress and spatial memory impairment. The Morris water maze was used to evaluate the cognitive functions of rats. Thiobarbituric acid reactive substances (TBARS), which are the indicators of lipid peroxidation, and the activities of antioxidative enzymes (glutathione peroxidase and superoxide dismutase) were measured in the rat hippocampus and prefrontal cortex which form interconnected neural circuits for spatial memory. Acute administration of ethanol significantly increased TBARS levels in the hippocampus. Combined melatonin-ethanol treatment caused a significant increase in glutathione peroxidase activities and a significant decrease of TBARS in the rat hippocampus. In the prefrontal cortex, there was only a significant decrease of TBARS levels in the combined melatonin-ethanol receiving group as compared to the ethanol-treated group. Melatonin did not affect the impairment of spatial memory due to acute ethanol exposure, but melatonin alone had a positive effect on water maze performances. Our study demonstrated that melatonin decreased ethanol-induced lipid peroxidation and increased glutathione peroxidase activity in the rat hippocampus.