Effect of cationic grafted copolymer structure on the encapsulation of bovine serum albumin.

The aim of the present study was to evaluate a library of poly-L-lysine (PLL)-graft (g)-polyethylene glycol (PEG) copolymers for the ability to encapsulate effectively a model protein, bovine serum albumin (BSA), and to characterize the stability and protein function of the resulting nanoparticle. A library of nine grafted copolymers was produced by varying PLL molecular weight and PEG grafting ratio. Electrostatic self-assembly of the protein and the grafted copolymer drove encapsulation. The formation of protein/polymer nanoparticles with a core/shell structure was confirmed using PAGE, dynamic light scattering, and electron microscopy. Encapsulation of the BSA into nanoparticles was strongly dependent on the copolymer-to-protein mass ratio, PEG grafting ratio, and PLL molecular weight. A copolymer-to-protein mass ratio of 7:1 and higher was generally required for high levels of encapsulation, and under these conditions, no loss of protein activity was observed. Copolymer characteristics also influenced nanoparticle resistance to polyanions and protease degradation. The results indicate that a copolymer of 15-30 kDa PLL, with a PEG grafting ratio of 10:1, is most promising for protein delivery.

The association of the microcystic, elongated and fragmented (MELF) invasion pattern in endometrial carcinomas with deep myometrial invasion, lymphovascular space invasion and lymph node metastasis.

The purpose of this study was to investigate the frequency of microcystic, elongated and fragmented (MELF) pattern of invasion in endometrioid endometrial adenocarcinomas (EA) and its association with prognostic factors. Stained tissue sections from 121 cases of EA (total hysterectomy and pelvic, with or without para-aortic, lymphadenectomy specimens) were reviewed to identify cases showing MELF-type invasion. The prognostic factors of low tumour grade, deep myometrial invasion (MI), cervical stromal involvement, lymphovascular space invasion (LVSI), lymph node (LN) metastasis and advanced clinical stage were more frequently observed in MELF-positive cases (p < 0.05). Thus, MELF-positive cases had an increased frequency (28/121) of these prognostic factors, which has implications in routine clinical practice, as it signals the importance of recognising MELF pattern invasion. In univariate analysis, MELF positivity, deep MI, cervical stroma involvement and LVSI were significantly related to LN metastasis (p < 0.05). However, in multivariate analysis, only MELF pattern invasion and cervical stroma involvement were independent factors for LN metastasis. Nevertheless, further studies are needed to evaluate the clinical significance of MELF pattern of invasion in endometrial adenocarcinoma.

The association of the cribriform pattern with outcome for prostatic adenocarcinomas.

With the revision of the Gleason system at the 2005 International Society of Urological Pathology Consensus Conference, there was consensus that most cribriform glands should be classified as pattern 4. There is now increased understanding that invasive cribriform carcinoma is a relatively aggressive disease. This study was based on 233 radical prostatectomy (RP) specimens collected at the Department of Pathology, Umraniye Education and Research Hospital, from 2006 to 2013. We assessed the cribriform foci associated with the more definitive patterns 3, 4, and 5 elsewhere on the RP specimens and evaluated the association of the presence of cribriform pattern (CP) with biochemical prostate-specific antigen recurrence (BPR). In Cox regression model, taking into account the Gleason score (GS), pathologic stage, surgical margin (SM) status, presence of a CP, and preoperative prostate-specific antigen (PSA), a positive SM, and the presence of a CP were independent predictors of BPR after RP. We observed BPR more frequently in GS 3+3 cases with a CP than in those without a CP (p=0.008). There was no significant difference in BPR status for cases with GS 3+4, 4+3, 4+5, and 5+4 when the patients were stratified by the presence of a CP. On the basis of these data, we suggest that the classification of CP into Gleason pattern 4 has value in predicting BPR status after RP. However, as many of these modifications are empirical and supported by only a few studies, long-term follow-up studies with clinical endpoints are necessary to validate these recommendations.

Increased oxidative stress in patients with essential thrombocythemia.

BACKGROUND: Essential thrombocythemia (ET) is a clonal disease in which thrombotic and hemorrhagic complications are common. Our aim in this study was to investigate whether oxidative stress in ET patients increased compared to healthy volunteers and to investigate whether there is a relationship between vascular events and oxidative status parameters in ET patients. PATIENTS AND METHODS: We determined the serum levels of oxidative status parameters, such as total oxidative status (TOS), total antioxidant status (TAS), oxidative stress index (OSI) and malondialdehyde (MDA) in ET patients. Forty-three ET patients (20 males, 23 females) and 20 healthy volunteers were enrolled. Oxidative status parameters of the patients were compared with those of the controls at time of diagnosis and at 6th-month follow-up. Additionally, oxidative status parameters of patients with ET with a history of vascular event were compared with patients without a vascular event history during diagnosis. RESULTS: Rises in TOS, OSI, and MDA were statistically significant in the patients group; however, the TAS value was significantly lower compared to the control group. Furthermore, TOS was significantly higher in patients with history of vascular event compared to the patients without such a history. Following therapy, OSI and MDA values were significantly reduced in the patient group compared to the pre-treatment values. CONCLUSIONS: Our findings reveal that although oxidative stress parameters were increased, compensative total antioxidant status was significantly reduced in ET patients. Furthermore, TOS values were significantly high in patients with a history of vascular event.

Effect of valsartan on erythropoietin and hemoglobin levels in stage III-IV chronic kidney disease patients.

Angiotensin-converting enzyme inhibitors (ACEIs) were accepted as a potential cause of inadequate epoetin response in chronic kidney disease (CKD) patients. We aimed to determine the effects of valsartan, an angiotensin receptor blocker (ARB), on serum ertyhropoietin levels and on certain biochemical and haematological parameters in hypertensive CKD patients. Twenty-two stage III-IV CKD patients (mean age; 56.8 +/- 8.9 years, 12 male 10 female) were included in the study. Before initiating the treatment, current anti-hypertensive treatments (if any) were discontinued, and blood samples were collected after a washout period of 3 weeks. Valsartan 80 mg/day was started, and additional anti-hypertensive agents were given according to study protocol if needed. One way Anova and paired t-tests were used for statistical comparisons. Serum blood urea nitrogen (BUN), creatinine, uric acid, potassium, haemoglobin and erythropoietin values were measured, and glomerular filtration rates were calculated before and 3, 6 and 90 days after valsartan treatment, a significant reduction in EPO level was observed at 3rd (19.6 +/- 24.0 vs. 13.8 +/- 8.5, p = 0.010), 6th (12.1 +/- 7.6, p = 0.009), and 90th days (8.3 +/- 5.4, p = 0.007). When pre-treatment values were compared with 90th day results, no significant change was observed in terms of hgb, htc, serum BUN, creatinine, uric acid, potassium, and GFR values. In conclusion, valsartan, an ARB, did not decrease haemoglobin levels in stage III-IV CKD patients despite significant reduction in serum erythropoietinlevels, so ARBs may be preferred to ACEIs in CKD patients when indicated.

Urinary beta-2 microglobulin in renal dysfunction associated with hypothyroidism.

Hypothyroidism is associated with a number of functional renal disorders primarily affecting water and salt handling. In this study, we aim to investigate functional renal disorders in overt and subclinical hypothyroidism. We utilised urinary beta-2 microglobulin (beta2M) as a sensitive marker of tubular dysfunction. Urinary beta2M excretion and tests for renal functions were repeated before and after T4 replacement therapy. Forty-four patients (28 with overt disease, 16 with subclinical disease) and 31 healthy control subjects were involved in the study. There was a significant increase in urinary beta2M in both overt and subclinical hypothyroidism (p < 0.05 in both). TSH levels were correlated with beta2M excretion. Effects of hypothyroidism on renal functions were readily reversible by 3 weeks of thyroid hormone replacement therapy. Urinary beta2M was a sensitive marker of renal tubular dysfunction associated with overt and subclinical hypothyroidism.

Tuberculosis in dialysis patients, single centre experience from an endemic area.

Because of immunity defect, patients with end-stage renal disease are at increased risk of developing infections, tuberculosis (TB) in particular. The incidence of TB is higher in dialysis patients than in general population. We retrospectively reviewed the charts of dialysis patients with TB in our facility. A total of 287 dialysis patients (153 male, 134 female, 223 haemodialysis (HD), 64 continuous ambulatory peritoneal dialysis (CAPD) patients, mean age 46 +/- 15) were reviewed from October 1997 to January 2002. TB developed in 30 patients (17 male, 13 female, 24 HD and six CAPD). Thirteen patients with TB presented with fever of unknown origin (FUO) and four of them subsequently developed military lesions on chest X-ray. Nine patients had pulmonary TB (four with pleural effusions), five patients had TB lymphadenits, two patients had TB peritonitis and one patient had vertebral TB. TB was presented mostly as FUO among dialysis patients in a region under poor socio-economic conditions. In such areas with endemic TB, dialysis patients who present with FUO should be carefully evaluated for the presence of TB, and test therapy for TB should be performed in otherwise unexplained FUO.

Clinical characteristics and genetic screening of an extended family with MEN2A.

MEN-2A is characterized by medullary thyroid carcinoma (MTC) with pheochromocytoma and sometimes parathyroid adenoma. In affected members of the family, the risk of MTC is about 100%. Biochemical screening allows tumors to be detected early but even at this stage treatment is not always curative. Missense mutations in exon 10 and 11 of the RET proto-oncogene are associated with MEN-2A. Early detection of this mutation by DNA analysis allows the identification of the carriers of the gene. We performed genetic screening in 88 members of an extended family with MEN-2A and found 18 members positive for RET mutation (Cys634Gly). Only three of these 18 RET positive cases had a previous diagnosis of medullary cancer and/or pheochromocytoma. Up to now, 12 of the RET positive cases have undergone thyroidectomy. There was extended disease with cervical lymph node metastasis in 6 of them, bilateral medullary microcancer in 3 and c-cell hyperplasia in the remaining 3. Three of the 18 RET positive patients had also pheochromocytoma. Primary hyperparathyroidism was present in only one patient. The mean age of diagnosis of medullary cancer was between 25-50 yr and mean age of death was between 35-95 yr in affected members of the family. The family had many other affected members in other cities in Turkey and in other countries throughout the world from Australia to the Netherlands. So this family is perhaps one of the most extended families with MEN-2A.

The effects of volatile anesthetics on the Q-Tc interval.

OBJECTIVE: To examine the effects of halothane, isoflurane, and sevoflurane on Q-Tc interval (corrected for heart rate) during inhalation induction of anesthesia. DESIGN: Prospective, double-blind, randomized study. SETTING: Departments of Cardiology and Anesthesiology in a university hospital. PARTICIPANTS: Patients undergoing noncardiac surgery. INTERVENTIONS: A total of 65 American Society of Anesthesiologists physical status I-II patients, aged 16 to 50 years, undergoing general anesthesia, were randomly allocated to receive halothane, isoflurane, or sevoflurane. MEASUREMENTS AND MAIN RESULTS: The time to reach the predetermined end-tidal concentrations of 3 minimum alveolar concentration was 6 to 10 minutes. When compared with preinduction values, heart rate decreased after halothane (p < 0.01) and sevoflurane (p < 0.05) administration; in contrast, heart rate increased after induction of anesthesia with isoflurane (p < 0.05). The mean QRS intervals were not significantly changed after halothane, isoflurane, or sevoflurane. The Q-Tc interval was increased with isoflurane compared with baseline (465 +/- 23 v 441 +/- 18 msec, p < 0.01), not changed with sevoflurane (441 +/- 17 v 434 +/- 19 ms, p > 0.05), and shortened with halothane (426 +/- 23 v 445 +/- 21 msec, p < 0.01). CONCLUSION: Sevoflurane or halothane may be preferred to isoflurane in patients with conditions that are known to induce a prolonged Q-Tc interval. The effects of Q-Tc interval changes resulting from different anesthetic agents on morbidity and the incidence of arrhythmias during anesthesia warrant further investigation.

Relationship Between Leptin Levels and Body Indexes in Patients with Haematologic Malignancy.

Leptin is a recently found hormone regulating body weight. In human obesity, this weight-regulating hormone level is in a positive correlation with FMI (fat mass index) and BMI (body mass index). In this study, we aimed to investigate the relation between serum leptin levels and BMI, PF (percentage fat), LMI (lean mass index), FMI and some other parameters of patients with haematologic malignant diseases. Fourty-four patients with haematologic malignant diseases and 25 healthy control group were taken into the study. In the comparison, there were no significant difference between the PF and FMI values of both groups, while the mean BMI and LMI values of the control group were significantly higher than that of the patient group. There was a positive correlation between leptin levels and BMI and FMI among parameters studied in our control group, whereas we couldn't demostrate any such correlation in patient group. We estimate that the alteration may be due to disturbances in the feed back mechanism developing in patient with haematologic malignancy.