Protective effect of magnesium preloading on cisplatin-induced nephrotoxicity: which dose is more suitable?

OBJECTIVE: Cisplatin is a widely used and potent cytotoxic chemotherapy agent, but its nephrotoxicity is a significant limiting side effect. Various premedication approaches have been implemented to preserve renal function, including magnesium (Mg) preloading. However, the optimal Mg dosage is still unknown. Our study aimed to assess the protective effects of different Mg doses as premedication in cisplatin-based chemoradiotherapy for patients with local/locally advanced cervical and head-neck cancers. PATIENTS AND METHODS: This retrospective, multicenter study involved premedication with saline infusion containing potassium chloride and magnesium sulfate (MgSO4) for all patients before cisplatin treatment. Patients were divided into two groups: 12 mEq MgSO4 (low-dose Mg preload group, low-Mg) and 24 mEq MgSO4 (high-dose Mg preload group, high-Mg). Renal function was evaluated using serum creatinine (sCr, mg/dl) and estimated glomerular filtration rate (eGFR, ml/min). Acute kidney injury (AKI) was defined per the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Renal outcomes and efficacy were compared between the groups. RESULTS: In the low-Mg group (n = 159), sCr levels were significantly higher compared to baseline, various weeks during treatment, and at the 1st, 3rd, 6th, and 12th months post-treatment (p < 0.001). In the high-Mg group (n = 128), no significant changes were observed during treatment and at 1st, 3rd, and 12th months post-treatment (p > 0.05). A significant reduction in mean sCr level from baseline to 6 months was noted in the high-Mg group (p < 0.001). eGFR values are generally correlated with sCr levels. AKI occurred in 21 (13.2%) and 22 (17.7%) patients in the low-Mg and high-Mg groups, respectively (p = 0.292). There was no difference in progression-free or overall survival between the groups. CONCLUSIONS: We clearly demonstrated that saline hydration with 24 mEql MgSO4 supplementation before cisplatin treatment has a better renal protective effect than 12 mEql MgSO4 without reducing efficacy, especially in patients with local/local advanced cervical and head-neck cancer receiving cisplatin with concurrent radiotherapy.

Resveratrol ameliorates hepatic injury and modulates hepatic biomarkers of regeneration, apoptosis and survival in a rat model of blunt hepatic trauma.

OBJECTIVE: To investigate the protective potential of resveratrol (RES) in blunt hepatic trauma (BHT) by exploring the anti-inflammatory and histopathologic effects as well as modulatory effects on hepatic biomarkers of acute injury, regeneration, apoptosis and survival in a rat model of BHT. METHODS: A total of 21 Wistar Albino rats (weighing 120-250 g) were separated into 3 groups (n = 7 for each group), namely control group (CON; standard feeding), BHT group (BHT; blunt hepatic trauma plus observation) and trauma plus BES group (BHT-RES; blunt hepatic trauma plus intraperitoneal injection of 10 mg/kg RES). Serum levels for aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and bilirubin were measured on Day 7 and rats were sacrificed for histopathological (inflammation scores) and immunohistochemical [expression of proliferation marker (Ki-67) and apoptosis-related markers (Bcl-2, and Bax)] analyses in resected liver tissue. RESULTS: The highest levels for serum AST (p = 0.002), ALT (p = 0.002) and LDH (p = 0.002) were obtained from BHT group of rats, as followed by BHT-RES and control groups, respectively. The highest scores for Ki 67 (p = 0.002 for each), Bcl 2 (p = 0.002 for each) and Bax (p = 0.002 for each) were obtained from BHT-RES group of rats, as followed by BHT and control groups, respectively. Inflammation scores were significantly higher in BHT vs BHT-RES group (2.42 ± 0.53 vs 1.42 ± 0.53; p = 0.001) and both groups had higher inflammation scores than the control group (0.0 ± 0.0; p = 0.001). CONCLUSION: In conclusion, our findings revealed for the first time that RES exerts promising hepato-ameliorative effects against blunt hepatic injury as evidenced by decreased inflammation scores, parallel with improved hepatic histology, decreased serum transaminase activity as well as enhanced modulatory effect on regenerative and apoptotic processes in RES-treated rats subjected to experimentally-induced blunt hepatic trauma (Tab. 1, Fig. 1, Ref. 37).

The Comparison of Inflammatory Responses and Clinical Results After Groin Hernia Repair Using Polypropylene or Polyester Meshes.

The aim of this study was to compare the clinical results and the inflammatory responses against polypropylene and polyester meshes after groin hernia repair. Ninety patients with unilateral inguinal hernia randomly underwent Shouldice herniorrhaphy or Lichtenstein hernioplasty using polypropylene or polyester meshes. Venous blood samples were collected to evaluate serum interleukin-6 (IL-6) and C-reactive protein (CRP) levels. Postoperative acute and chronic pain and time to attain to normal activities were evaluated. IL-6 levels decreased to preoperative levels in all groups at 48th hour. CRP levels of mesh-implanted groups are significantly higher than preoperative level at 48th hour, while it reduced to preoperative level in Shouldice herniorrhaphy group. Patients treated with mesh repair had less postoperative acute pain and recovered more rapidly than those who underwent Shouldice herniorrhaphy. It was concluded that polypropylene and polyester meshes used in hernia repair caused similar inflammatory responses and that clinical results after groin hernia repair with these prostheses were not significantly different.

The effect of different suture materials on the safety of colon anastomosis in an experimental peritonitis model.

BACKGROUND: The aim of this experimental study was to compare the safety of different suture materials in a left colonic anastomosis in the presence of peritonitis. MATERIALS AND METHODS: Twenty-one male Wistar albino rats were randomly divided into three groups. First, left colonic injuries were created in all groups for the peritonitis model. After 24 hours, coated polyglactin 910 and silk suture were used in Group I rats, polydioxanone and silk suture were used in Group II rats, and coated polyglactin 910 plus antibacterial suture and silk suture were used in Group III rats during colonic anastomosis. Tissue hydroxyproline, anastomotic bursting pressure, and histopathologic findings on the anastomosis line were evaluated on the 10th postoperative day by performing a relaparatomy. RESULTS: The mean bursting pressure values were 198 ± 11.37, 220 ± 17.7, and 244 ± 9.52 in Groups I, II, and III, respectively (Group I vs. II, p < 0.035; I vs III, p < 0.002; and II vs III, p < 0.021). The mean hydroxyproline levels were 1.21 ± 0.58, 1.47 ± 0.44, and 2.11 ± 0.32 in Groups I, II, and III, respectively (Group I vs II, p < 0.338; I vs III, p < 0.011; and II vs III, p < 0.025). When histopathologic findings of the groups were compared, the healing score of the intestinal tissue was higher in Group III than in Group I (p < 0.015), whereas there were no statistically significant differences among Groups I vs II and II vs III (p < 0.081 and p < 0.095, respectively). CONCLUSION: Antibacterial suture usage increased anastomosis safety in the presence of peritonitis in resection and primary anastomosis.

[The effects of L-tryptophan and pentoxiphylline on stress ulcer]. / L-triptofan ve pentoksifilinin stres ulseri uzerine etkisi.

BACKGROUND: It is well known that stress leads to the formation of gastric mucosal lesions. Free oxygen radicals play an important role in the pathogenesis of inflammation and tissue damage. It was observed that L-tryptophan has a positive effect on gastric mucosal damage in ischemia-reperfusion injury by inhibition of free oxygen radicals. The protective effect of pentoxifylline was shown in gastric mucosal damage induced by ischemia - reperfusion or the application of some topical agents. We performed an experimental study to determine whether intragastric L-tryprophan and intramuscular pentoxifylline protect gastric mucosal damage that is induced by immobility stress. METHODS: Forty rats were immobilized and divided into four groups. No treatment was made in the first group; in group 2,3 and 4, L-tryptophan, pentoxifylline and L-tryptophan + pentoxifylline were administered, respectively. The gastric lesions were assessed macroscopically and microscopically two hours following treatment. RESULTS: In the second and fourth groups, the lesion surface area and average mucosal damage were fewer in comparison to the control group (p<0,03). Moreover, an histopatologically improvement in the surface epithelium was observed in these groups. The average lesion score also reduced significantly (p<0,03) only in the L-tryptophan group. On the other hand, no statistically significant improvement was observed in the pentoxifylline group. CONCLUSION: As a result, it was concluded that L-tryptophan could play a protective role in the gastric mucosal damage associated with stress.

The effects of melatonin and prostaglandin E1 analogue on experimental hepatic ischaemia reperfusion damage.

The effects of antioxidant melatonin and a prostaglandin E1 analogue (PGE1) on hepatic ischaemia reperfusion damage were investigated. Fifty rats were divided into five equal groups: sham, control, melatonin, PGE1 and combined treatment. No procedures were applied to the sham group. In the control and treatment groups, the hepatic hilus was clamped at the level of the hepatic artery and portal vein for 60 min and reperfusion was provided for two hours. In the treatment and combined treatment groups, melatonin was administered intramuscularly at a dose of 20 mg/kg 15 mins before reperfusion, and PGE1 was administered intravenously at a dose of 25 mg/kg 1 min before reperfusion. Blood samples for SGOT, SGPT, GSH-Px, SOD and MDA measurements and hepatic tissue samples were taken. The decrease in the plasma MDA levels was statistically significant in the melatonin and combined treatment groups, but not in the PGE1 group (p > 0.025). A significant decrease was found in the tissue MDA levels of the treatment groups (p < 0.025). The decrease in SGOT and SGPT levels in the PGE1 group was significant (p < 0.025), but the decreases in the melatonin and combined treatment groups were not significant (p>0.025). Melatonin and PGE1 were found to be effective in reducing the hepatic ischaemia reperfusion damage in rats. However, the damage could not be reversed. Combined treatment was found not to be superior to melatonin or PGE1 alone.

Effects of melatonin and lactulose on the liver and kidneys in rats with obstructive jaundice.

The negative effects of obstructive jaundice (OJ) on the liver and kidneys cause high morbidity and mortality. In this study, the effects of melatonin (M) and lactulose (L) on the liver and kidneys were investigated by inducing OJ in 30 rats in five groups (n = 6): controls, sham, M, L, and M + L. In the treatment group, after the rats' biliary canals were tied and cut, 10 mg/kg M IM and 2 ml/day L p.o. was administered for 7 days. The histopathologic findings in the liver and kidneys, tissue malonyl dialdehyde (MDA) levels, and serum biochemistry were evaluated. In the M group, pathological histologic findings were less marked than in the other groups; investigation of kidney cross-sections revealed no significant differences among groups. In the jaundiced rats liver MDA levels were significantly higher compared to the control group ( P < 0.001), but no such difference was observed in kidney MDA levels ( P > 0.05). L did not cause any significant changes in tissue MDA levels. There were no differences among groups with regard to serum levels of liver enzymes and bilirubin. Serum urea was significantly less in the group that received L ( P < 0.001), but the groups showed no significant differences with respect to creatinine values ( P > 0.05). The increase in serum total cholesterol was significantly less in the M + L group than in the other groups ( P < 0.001). We conclude that in the rats in which obstructive jaundice was induced, M administration reduced liver and kidney injury, but L and M + L did not lead to significant improvement.

Immunological follow-up of hydatid cyst cases.

Hydatid disease is caused by Echinococcus granulosus. In this study, we aimed to investigate the benefit of monitoring cases with hydatid cyst by means of immune components in patients in a long-term follow-up after surgery. Eighty-four preoperative and postoperative serum samples from 14 cases undergoing surgery for hydatid disease were evaluated in terms of immune parameters, such as total and specific IgE, IgG, IgM, IgA and complement. Total and specific IgE were determined by ELISA. Specific IgG levels were measured by indirect hemagglutination. Total IgG, IgM, IgA and complement (C3 and C4) were detected by nephelometry. Imaging studies were also carried out during the follow-up. In none of the patients hydatid cysts were detected during the follow-up. Total IgE levels in the sera of the patients decreased to normal six months after surgery. Although specific IgE against echinococcal antigens decreased one year after operation, levels were still significantly high. There were no changes in the levels of anti-Echinococcus IgG and total IgG in follow-up period. Additionally, other parameters, such as IgA, IgM, C3 and C4, were not affected.

Nonspecific ulcerated jejunitis as an unusual complication of laparoscopic cholecystectomy: report of a case.

We describe herein the case of a 65-year-old man in whom a lower gastrointestinal hemorrhage developed a few days after he underwent an elective laparoscopic cholecystectomy. A laparotomy was performed on postoperative day 16 and a jejunal segment containing mucosal changes and oozing ulcers was resected. Pathologic examination of the specimen revealed "nonspecific ulcerated jejunitis." There is no explanation for the etiopathogenesis of this pathology; however, we concluded that this clinical picture may be attributed to ischemia-reperfusion injury that occurred following an ischemic period caused by the pneumoperitoneum during laparoscopic surgery.

Effect of levamisole on intestinal anastomoses in transfused guinea pigs.

In this experimental study, the effects of an antihelminthic and immunostimulating agent (levamisole) on anastomosis recovery in transfused and normal guinea pigs were investigated. A total of 56 animals were divided into four groups of 14 each; an additional 10 were employed for blood transfusion (BT). Intestinal anastomoses were performed on all animals; the following postoperative treatments were administered: none (control group); BT; intra-abdominal (IA) levamisole; and BT + levamisole. After recording the mortality of each group, a relaparotomy was performed on one-half of the animals on the 3rd postoperative day and on the remaining half on the 7th postoperative day. Findings of IA sepsis, resistance of the anastomosis, bursting pressure, and hydroxyproline values were evaluated. Statistical comparison of the groups was accomplished by analysis of variance. In the transfused group an increase in sepsis was determined and the bursting pressure was significantly lower than in the control group. IA levamisole application following BT reduced the mortality by diminishing IA sepsis and anastomotic abscess formation and increased anastomotic pressure and recovery (P < 0.01). Histopathologic recovery in levamisole groups was better than in the group that received BT only. Levamisole application without BT resulted in equal mortality and morbidity to that of the control group. We conclude that clinical use of levamisole should be considered only in intestinal anastomoses in which BT is inevitable.

Sigmoid colon perforation due to geophagia.

Geophagia can be a problem in mentally handicapped patients. This case report presents a 71-year-old mentally handicapped women who had to be operated in emergency for colonic perforation due to geophagia.

Effects of L-thyroxine and zinc therapy on wound healing in hypothyroid rats.

Unfavourable effects of hypothyroidism and zinc deficiency on wound healing are well known. This experimental study was conducted on rats to evaluate the effects of hormone replacement and zinc supplement on wound healing. A total of 50 rats were divided into 5 groups of 10 rats as follows: Control group (A), a hypothyroidism group (B), a L-thyroxine receiving hypothyroidism group (C), a zinc receiving hypothyroidism group (D), and a L-thyroxine plus zinc receiving hypothyroidism group (E). In order to develop hypothyroidism, 5-propyl 2-thiouracil had been given intraperitoneally for a period of 21 days to all groups except the control group. A laparotomy with a 4 cm median incision was performed in all rats. The first half of the rats was sacrificed on the 7th day and the remaining on the 14th day. Breaking strength, hydroxyproline concentrations in the healing scar tissue and blood serum zinc levels were measured. Although both values--breaking strength and hydroxyproline levels--, compared to all others, were found to be higher in the L-thyroxine plus zinc receiving group (group E) on the 7th day, differences among the groups were not statistically significant. However, on the 14th day, these differences were found to be significant. We conclude that the hormone replacement therapy in hypothyroidism cases was beneficial with regard to wound healing and the results were more satisfactory if zinc was added to the therapy.

Fascioperitoneal graft with T-tube drainage for patching bile duct defects.

Reconstruction of choledochal wall defects in an experimental dog model by T-tube plus fascioperitoneal graft and an evaluation of the short-term results were the aims of this study. Twelve randomly selected mongrel dogs of both sexes, having an average weight of 22.15 +/- 1.85 kg, were anaesthetized with ketamine HCI and xylazine and underwent laparatomy. The front wall of choledoch canal were excised with its all layers 0.5 cm in diameter at the distal part of the cystic duct junctions. These defects were repaired by using grafts prepared of the same diameter from the dorsal fascias of rectus muscles and peritoneum. T-tubes were introduced into the common ducts on the proximal part of the grafts. One of the animals died in the postoperative period due to evantration. T-tube cholangiograms on the twelfth day did not indicate any extravasation or stricture. Histopathological examination of the graft regions on the sixtieth day revealed that the epithelialization had commenced on the border between the bile epithelium and grafts. Based on these early findings, it was suggested that if supported by further studies it may be thought of as a clinical method.