Oxidative stress parameters and keap 1 variants in T2DM: Association with T2DM,diabetic neuropathy,diabetic retinopathy,and obesity

IntroductionChronic hyperglycemia activates the inflammatory pathways and oxidative stress mechanisms with consequent damage to nerve tissue and retina. The Keap1‐Nrf2 pathway acts as one of the most important antioxidant pathways of the organism. Variants of Keap1 could affect susceptibility to diabetes and its complications.MethodsIn a case‐control study, 400 individuals included type 2 diabetes mellitus (T2DM) patients without complication, with neuropathy, with retinopathy, and healthy individuals were investigated. The levels of glutathione (GSH), glutathione peroxidase (GPx), malondialdehyde (MDA), and total antioxidant capacity (TAC) were measured using chemical methods. Using the PCR‐RFLP method, the Keap1 (rs11085735) variants were identified.ResultsNeuropathic patients had significantly lower levels of GSH, GPx, and TAC and higher levels of total oxidative status (TOS), MDA, and oxidative stress index (OSI) compared to T2DM patients without complication and controls. Lower levels of GSH and GPx and a higher level of MDA were observed in patients with retinopathy compared with controls. Obesity was associated with significantly lower GPx activity and higher TOS. A significantly higher Keap1 AA genotype was found in patients with neuropathy than T2DM without complication and controls. The presence of Keap1 AA genotype correlated with lower GPx activity compared to CC genotype.ConclusionsOur study suggests the role of reduced antioxidant system and Keap1 variants in the pathogenesis of T2DM and its complications of neuropathy and retinopathy and also obesity in enhanced oxidative stress. Monitoring oxidative stress parameters in diabetic patients, especially those with complication and their treatment with antioxidants is suggested.     

A giant early second‐trimester placental chorioangioma associated with isolated proteinuria and histopathologically confirmed placental insufficiency,a novel association: A case report

We present a case of giant chorioangioma at 18 weeks of gestation leading to fetal hypertrophic cardiomyopathy without other evidences of fetal volume overload and late‐onset isolated proteinuria. Oligohydramnios developed at term and placental insufficiency was confirmed on histopathological examination and a nonanemic nonthrombocytopenic normal weight healthy baby was delivered.     

Endotoxin potentiates hepatocyte apoptosis in cholestasis

BACKGROUND:

Cholestasis is a component of liver disease of almost any etiology, including septic liver injury. The cellular mechanisms of liver injury in cholestasis and sepsis remain unresolved. We evaluated apoptosis, a well-orchestrated and potentially reversible mechanism of cell death, in bile duct-ligated and endotoxin-injected rats.

STUDY DESIGN:

Male Sprague-Dawley rats were randomly assigned to six groups (n = 6–9): bile duct-ligated+endotoxin (B+E), sham+endotoxin (S+E), bile duct-ligated (B), sham (S), endotoxin (E), and normal (N). On day 1, the bile ducts of B+E and B rats were ligated and severed. S+E and S animals underwent biliary manipulation only. On day 3, B+E, S+E, and E groups received 3 mg/kg endotoxin IV. On day 4, livers from all rats were excised, fixed, and stained (hematoxylin and eosin and terminal deoxynucleotidyl transferase dUTP nick-end labeling [TUNEL]). Portions were frozen for DNA fragmentation analysis. Caspase 3 activity was determined using isolated hepatocytes.

RESULTS:

Livers from all groups (B+E, S+E, E, and B) except normal and sham displayed apoptosis by hematoxylin and eosin staining, TUNEL staining, and DNA fragmentation. Histologic evaluation revealed 10% to 20% necrosis in endotoxin-treated animals (B+E, S+E, and E). Caspase 3 activity was significantly higher in endotoxin-treated animals versus animals without endotoxin (treated 0.450 ± 0.08 versus nontreated 0.135 ± 0.05, p < 0.0001) (mean ± SD).

CONCLUSIONS:

Cholestatic livers had apoptosis without progression to necrosis. When exposed to the second insult of endotoxin, cholestatic livers received an acute on chronic apoptotic trigger, and proceeded to necrosis. Endotoxin was a potent hepatotoxic insult because all treated rat livers displayed both apoptosis and necrosis.     

Polypoid endometriosis: a clinicopathologic analysis of 24 cases and a review of the literature

We describe 24 cases of polypoid endometriosis, most of which were referred because of problems in differential diagnosis, particularly distinction from a low-grade müllerian neoplasm. The patients were 23 to 78 years (mean 52.5 years) of age. Seven patients were on unopposed estrogen, four on combined estrogen-progestin therapy, and one patient had a synchronous ovarian thecoma. The most common clinical presentations were a pelvic mass, vaginal polypoid masses, and large bowel obstruction. In some cases, the intraoperative findings suggested a neoplasm. Sites of involvement in order of frequency included colon, ovary, uterine serosa, cervical and/or vaginal mucosa, ureter, fallopian tube, omentum, bladder, paraurethral and paravaginal soft tissue, and retroperitoneum. Multiple sites were involved in seven cases. Five cases occurred within ovarian or extraovarian endometriotic cysts. The lesions ranged up to 14 cm in size and formed polypoid, pink, gray or tan, masses. On microscopic examination, the polypoid masses were composed of an admixture of endometriotic glands and stroma. A variety of glandular architectural patterns were observed, sometimes in combination, most commonly cystic and noncystic simple hyperplasia, but also simple or complex hyperplasia with atypia, disordered proliferative, and cystic atrophy. Various types of epithelial metaplasia (tubal, mucinous, squamous, papillary syncytial metaplasia) were common. Hemorrhage, fibrosis, prominent thick-walled blood vessels, hemosiderin-laden histiocytes, and decidual change were also present in some cases. Eighteen cases were associated with usual (nonpolypoid) endometriosis. In one case, polypoid endometriosis merged with a mucinous borderline tumor of endocervical-type. In all but two cases, polypoid endometriosis lacked periglandular stromal hypercellularity, stromal atypia, and intraglandular stromal papillae, helping distinguish it from adenosarcoma. Focal intraglandular stromal papillae were noted in two cases with focal mild periglandular stromal hypercellularity in one of them, but no stromal atypia was present in either case. Follow-up data in 17 patients indicated that 15 patients were alive without evidence of residual disease, 1 was alive with residual endometriosis, and 1 died of other causes. In conclusion, polypoid endometriosis is a rare manifestation of endometriosis that may be mistaken for a neoplasm on clinical, intraoperative, or pathologic assessment. Some cases may be attributable to exogenous hormones or hyperestrinism and, like conventional endometriosis, some may evolve into a premalignant or, rarely, a neoplastic lesion. The main lesion in the differential is a müllerian (mesodermal) adenosarcoma.     

Metarrhizium anisopliae as a Cause of Sinusitis in Immunocompetent Hosts

Metarrhizium anisopliae is a common pathogen of insects and has even been used to control insect populations. It is rarely isolated from human or animal sources, but recently, there have been three reported cases of disease, two in humans and one in a cat. We present our experience with five isolates from human sources, including two that were the apparent causes of two cases of sinusitis in immunocompetent hosts. The first patient was a 36-year-old male with frontal and ethmoid sinusitis, and the second was a 79-year-old female with chronic sinusitis. Both patients underwent surgery, and pathology of the surgical specimens revealed branching hyphae. Cultures grew only Metarrhizium species. Neither patient received antifungal therapy, and both did well postoperatively. The other three isolates were cultured from bronchoalveolar lavage specimens but were not felt to be clinically significant. Antifungal susceptibility testing using the National Committee for Clinical Laboratory Standards macrobroth method revealed that all isolates were resistant to amphotericin B, 5-flucytosine, and fluconazole. Itraconazole and newer azole compounds were more active. Metarrhizium species may cause disease in humans, even those without evidence of immunosuppression, and are apparently highly resistant to amphotericin B in vitro.     

Medium‐dose‐rate brachytherapy for cancer of the cervix: Preliminary results of a designed schedule

Aim: This retrospective analysis aims to report results from patients with cervical cancer treated by external beam radiation (EBR) with telecobalt and medium‐dose‐rate (MDR) brachytherapy and to establish the magnitude of brachytherapy dose reduction. Methods: Between June 2003 and September 2005, 77 patients with histological diagnosis of cervical carcinoma were treated with cobalt for external beam radiation, followed by one or two insertions of MDR with a dose rate from 220 ± 10 cGy/h. Median dose of EBR at whole pelvis was 50 Gy and the planned MDR schedule consisted of 1 or 2 insertions with 10–12 Gy to point A. Results: 77 patients were followed for median of 15 months (range: 1–33 months). Local control was achieved in 63 patients 81.8%. Local failure and overall failure rates were 11.7% and 19.5%, respectively. Overall incidence of rectal and bladder complication was 9.0% (7/77) and 7.8% (6/77), respectively. Conclusion: Results of this series suggest that use of telecobalt for EBR together with MDR brachytherapy with a dose reduction around 20% in comparison with low‐dose‐rate (LDR) brachytherapy can be an acceptable technique, especially in developing countries.     

Is Transesophageal Echocardiography Necessary before D.C. Cardioversion in Patients with a Normal Transthoracic Echocardiogram?

PURPOSE: Transesophageal echocardiography has emerged as an accepted approach before D.C. cardioversion for atrial fibrillation. The frequency of atrial thrombi detected on transesophageal echocardiography has varied from 7% to 23%. Many patients undergoing transesophageal echocardiography have had a previous transthoracic echocardiogram. Though transthoracic echocardiography has a low yield for the detection of intracardiac thrombi, it is highly accurate in diagnosing a structurally abnormal heart. The purpose of this study was to assess the frequency of thrombi detected by transesophageal echocardiography in patients with an entirely normal transthoracic echocardiogram and hence the advocacy of a selective approach in performing transesophageal echocardiography in patients undergoing D.C. cardioversion for atrial fibrillation. METHODS: 112 consecutive patients with atrial fibrillation who had undergone transesophageal echocardiography before D.C. cardioversion were evaluated. They all had a transthoracic echocardiogram within the 2 months preceding their transesophageal echocardiogram. Based on their transthoracic echocardiographic study, they were divided into two groups: Group 1 consisted of patients with a normal transthoracic echocardiogram and Group 2, those with an abnormal study. RESULTS: Thrombi or spontaneous echo contrast were found in 14 of 112 patients (16%). All however were detected in Group 2 patients. There was no patient with a normal transthoracic echocardiogram who had thrombus on his/her transesophageal echocardiogram. CONCLUSIONS: Our results suggest that a selective approach may be exercised in the use of transesophageal echocardiography prior to D.C. cardioversion for atrial fibrillation. Patients with an entirely "normal" transthoracic echocardiogram may proceed directly to cardioversion without a precardioversion transesophageal echocardiogram.