Expression of transient receptor potential vanilloid 4 and effects of ruthenium red on detrusor overactivity associated with bladder outlet obstruction in rats

Purpose

To investigate transient receptor potential vanilloid 4 (TRPV4) expression and the effects of ruthenium red (RR)—TRPV antagonist—on detrusor overactivity (DO) associated with bladder outlet obstruction (BOO).

Methods

Rats were randomly assigned to 3 groups. The control group (n = 10) included sham-operated rats. The BOO-group without RR (n = 15) and BOO-group with RR (n = 15) underwent partial BOO surgery. Three weeks postoperatively, cystometrography was performed in all rats. After confirming DO, RR was instilled intravesically in the BOO-group with RR. Urodynamic parameters were investigated, including contraction interval (CI) and contraction pressure (CP). TRPV4 expression was evaluated through immunofluorescence staining and western blotting.

Results

The BOO-group without RR had significantly shorter CI and significantly higher CP compared to the control. In the BOO-group with RR, CI was significantly longer compared to the BOO-group without RR. However, change in CP between BOO-group without and with RR was not significantly different. Immunofluorescence staining showed that TRPV4 was localized in the urothelium and detrusor muscles. TRPV4 immunofluorescence signals were increased in the urothelium and detrusor muscle in BOO-group without RR, compared with the control. In western blot analysis, immunoreactive bands indicating expression of TRPV4 were detected in the urothelium and detrusor muscle, and those were significantly increased in the BOO-group without RR compared with the control in the urothelium and detrusor muscle.

Conclusions

TRPV4 plays an important role in the pathophysiology of DO, and RR has a beneficial effect on DO associated with BOO.     

Effect of a recombinant manganese superoxide dismutase on prevention of contrast-induced acute kidney injury

Background

Contrast media (CM)-induced nephropathy (CIN) is an acute deterioration of renal function following administration of CM mediated to a large extent by the increased production of ROS within the kidney. Aim of this study was to evaluate whether a novel isoform of a recombinant Manganese SOD (rMnSOD) could provide an effective protection against CIN; this molecule shares the same ability of physiological SODs in scavenging reactive oxygen species (ROS) but, due to its peculiar properties, enters inside the cells after its administration.

Methods

We studied the effects rMnSOD on oxidative damage in a rat model of CIN in uninephrectomized rats, that were randomly assigned to 3 experimental Groups: Group CON, control rats treated with the vehicle of CM, Group HCM, rats treated with CM and Group SOD, rats treated with CM and rMnSOD.

Results

In normal rats, pretreatment with rMnSOD, reduced renal superoxide anion production, induced by the activation of NAPDH oxidase, by 84 % (p < 0.001). In rats of Group HCM, ROS production was almost doubled compared to rat of Group CON (p < 0.01) but returned to normal values in rats of Group SOD, where a significant increase of SOD activity was detected (+16 % vs HCM, p < 0.05). Administration of CM determined a striking fall of GFR in rats of Group HCM (?70 %, p < 0.001 vs CON), greatly blunted in Group SOD (?28 % vs CON, p < 0.01); this was associated with a lower presence of both tubular necrosis and intratubular casts in SOD-treated rats (both p < 0.01 vs Group HCM).

Conclusions

Our data indicate that rMnSOD is able to reduce renal oxidative stress, thus preventing the reduction of GFR and the renal histologic damage that follows CM administration.     

Sentinel Node Location in Trunk and Extremity Melanomas: Uncommon or Multiple Lymph Drainage Does Not Affect Survival

Background

Patients with cutaneous melanoma (CM) on the trunk have a worse prognosis than those with extremity CM. One reason could be multiple or uncommon (outside axilla or groin) sentinel node locations (SNLs).

Methods

We identified 859 patients who underwent sentinel node biopsy for trunk (n = 465) or extremity (n = 394) CM in three Swedish healthcare regions from 2000 to 2008. We collected patient, tumor, and sentinel node characteristics through clinical registers and medical records. We investigated the distribution of SNLs in a logistic regression model, and risk of overall and melanoma-specific death through 2011 in a multivariable Cox regression model.

Results

Trunk CM was associated with multiple SNLs (31 vs. 7 %; odds ratio [OR] 7.1; 95 % confidence interval [CI] 4.6–11.5; p < 0.001) but not uncommon SNLs (8 vs. 7 %; OR 1.1; 95 % CI 0.6–1.9; p = 0.75) compared with extremity CM. The increased risk of melanoma-specific death was confirmed for trunk CM (hazard ratio [HR] 1.9; 95 % CI 1.3–2.9; p = 0.003), especially on the upper back (HR 2.3; 95 % CI 1.4–3.6; p < 0.001) compared with extremity CM. Uncommon SNLs (HR 0.5; 95 % CI 0.2–1.4; p = 0.21) or multiple SNLs (HR 1.1; 95 % CI 0.4–2.9; p = 0.81) were not associated with melanoma-specific death compared with those with common/single SNL.

Conclusions

Trunk melanomas were associated with multiple lymph drainage, but the worse prognosis of trunk melanomas could not be explained by the increased frequency of multiple or uncommon SNLs.     

Prognostic Factors in Elderly Osteosarcoma Patients: A Multi-institutional Retrospective Study of 86 Cases

Background

The occurrence of osteosarcoma in elderly patients has recently been increasing, and the outcome is poor. This multi-institutional retrospective study was conducted to investigate clinical features and prognostic factors in patients older than 40 years with osteosarcoma.

Methods

Patients with conventional high-grade osteosarcoma older than 40 years were recruited to this study. Secondary osteosarcoma arising from Paget’s disease or irradiated bones was excluded. Information on tumor- and treatment-related factors was collected and statistically analyzed. The median follow-up was 57 months (range 8–244 months) for all surviving patients.

Results

A total of 86 patients were enrolled in this study. The median age at diagnosis was 61 years. Surgery and chemotherapy were conducted in 73 and 63 % of all patients, respectively. The 5-year overall and event-free survival rates were 38.8 and 34.0 %, respectively. Tumor site (extremity 57.9 %; axial 19.0 %; p < 0.0001), metastasis at diagnosis (yes 12.2 %; no 48.3 %; p < 0.0091), and definitive surgery (yes 56.2 %; no 10.6 %; p < 0.0001) were associated with overall survival. Although patients without metastasis who received definitive surgery were regarded as good candidates for chemotherapy, the addition of chemotherapy did not have any impact on the outcome (yes 63.4 %; no 65.2 %; p = 0.511).

Conclusions

The present study revealed the distinct clinical features, such as the high incidence of truncal tumors or metastasis at diagnosis, in patients older than 40 years with osteosarcoma. Additionally, prognostic factor analyses revealed that tumor site, metastasis at diagnosis, definitive surgery, and surgical margins were significant prognostic factors, whereas chemotherapy did not influence survival.     

Correlation Between Fluid–Fluid Levels on Initial MRI and the Response to Chemotherapy in Stage IIB Osteosarcoma

Background

The presence of fluid–fluid levels (FFLs) on osteosarcoma magnetic resonance imaging (MRI) is underestimated as a nonspecific finding; however, we hypothesized that FFL in conventional osteosarcoma may be indicative of chemoresistance.

Methods

In 567 stage IIB osteosarcoma patients, we evaluated the following: the incidence of FFL and their correlation with other clinicopathological variables; tumor volume change after chemotherapy and survival according to the presence of FFL; and the relationship between survival and the extent of FFL.

Results

One hundred eight (19 %) tumors showed FFL on initial MRI. FFL were correlated with proximal humeral location (P = 0.017), osteolytic on plain radiographs (P < 0.001), tumor enlargement after chemotherapy (P < 0.001), and poor histological response (P = 0.005). Large tumor (P < 0.01), proximal tumor location (P = 0.01), and presence of FFL (P < 0.01) were independent predictors of poor survival. Compared to the extensive FFL (more than one third of the tumor), small foci of FFL (less than one third of the tumor) showed a high tendency for tumor enlargement after chemotherapy (P < 0.001), poor histologic response (P = 0.001), and worse survival (P < 0.001).

Conclusions

FFL on initial MRI could predict tumor progression after chemotherapy. Notably, tumors with small foci of FFL (less than one third of the tumor) have a high propensity for poor outcome. Patients with this finding should be considered for risk-adapted therapy.     

Outcome Prediction of Pulmonary Metastasectomy Can Be Evaluated Using Metastatic Lesion in Osteosarcoma Patients

Background

We investigated whether molecular prognostic factors should be evaluated in specimens of the primary or the metastatic lesion and if the prognosis after initial pulmonary metastasectomy can be predicted based on evaluation of metastatic lesion specimens in osteosarcoma patients.

Methods

This retrospective study included 29 osteosarcoma patients with pulmonary metastases (19 males, 10 females; age 21 ± 10 years). Molecular prognostic factors were the levels of vascular endothelial growth factor type A (VEGF-A), VEGF type C (VEGF-C), and Ki67. Primary and pulmonary metastatic lesions could be compared in 18 patients regarding the values of marker expressions and the prognosis after initial pulmonary resection. Finally, the prognosis of all 29 cases was compared according to the molecular markers of the metastatic lesions.

Results

Evaluation of the metastatic lesions reflected the prognosis after pulmonary metastasectomy more than that of the primary lesions. In the metastatic lesions, positive expression of VEGF-A (n = 15), VEGF-C (n = 2), and Ki67 (n = 15) was associated with a significantly poorer prognosis (p = 0.0013, 0.0001, and 0.037, respectively). No patients with positive expression of both VEGF-A and Ki67 (n = 7) survived more than 5 years after the initial pulmonary resection. All patients who had negative reactions to both VEGF-A and Ki67 (n = 6) were alive at the end of the study.

Conclusions

Molecular prognostic factors should be investigated in specimens of the metastatic lesion. Combined evaluation of VEGF-A and Ki67 and of VEGF-C using pulmonary metastatic lesion specimens in osteosarcoma patients effectively reflects survival after pulmonary metastasectomy.     

Distribution and function of the endocannabinoid system in the rat and human bladder

Introduction and hypothesis

Our aim was to compare expression and distribution of cannabinoid receptors CB1 and CB2, transient receptor potential vanilloid receptor 1 (TRPV1), and modulating enzymes in human and rat bladder. We also evaluated effects of cannabinoid agonists (ACEA, agonist of CB1; GP1A, agonist of CB2) on contractile responses of rat bladder strips.

Methods

Distribution and expression of CB1, CB2 and TRPV1 receptors and enzymes fatty acid amide hydrolase (FAAH) and N-acyl phosphatidylethanolamine-hydrolyzing phospholipase D (NAPE-PLD) was studied using immunohistochemistry and immunoblotting on human and Wistar rat bladders. The effects of cannabinoid agonists on contractile responses of isolated rat bladder strips to electrical-field stimulation (EFS) or carbachol-evoked responses were determined.

Results

Immunoreactivity for CB1 and TRPV1 receptors and FAAH and NAPE-PLD was present in the bladder of both species. CB1 proteins were of different sizes in rat (57 kDa) and human (40 kDa) bladder. CB2 (45 kDa in both species) immunolocalised to both urothelium and detrusor muscle in human bladder but only to detrusor muscle in rat. FAAH proteins were found at 55 kDa for both species. Rat NAPE-PLD protein (44 kDa) was similar in size to that in human bladder (45 kDa). TRPV1 proteins were found at 104 kDa in both species. ACEA (10^?4?M) attenuated bladder contractions by 35?±?5.4 % (p?<?0.001); GP1a had no effect despite the EC₅₀ values for the carbachol dose–response curves for both agonists being significantly shifted to the right.

Conclusions

The endocannabinoid system is functionally expressed in both species, with CB1 receptors showing both pre- and postsynaptic inhibitory effects on rat bladder contraction, whereas CB2 acts only postsynaptically.     

Tumor Volume Increase During Preoperative Chemotherapy as a Novel Predictor of Local Recurrence in Extremity Osteosarcoma

Background

Known risk factors (surgical margin, tumor necrosis) of local recurrence (LR) in osteosarcoma are determined by results available after surgery. However, relations between preoperative characteristics and LR have not been clearly defined.

Methods

We compared the clinicopathologic characteristics of 36 osteosarcoma patients with LR and 394 patients without LR after surgery. In addition, prognostic variables were evaluated to establish factors could influence LR.

Results

Compared to the non-LR group, the LR group showed an increase in tumor volume ratio (TVR) during preoperative chemotherapy (P < 0.01), inadequate surgical margin (P < 0.01), and poor histologic response (P < 0.01). Univariate analysis of data from 430 patients revealed that an increased TVR (P < 0.01), inadequate surgical margin (P < 0.01), poor histologic response (P < 0.01), and nonosteoblastic pathologic subtype (P = 0.04) were negatively related to LR-free survival. In multivariate analysis, an elevated TVR (P < 0.01, relative risk = 10.26) and inadequate surgical margin (P < 0.01, relative risk = 5.91) emerged as the key prognostic factors for LR.

Conclusions

A TVR increase during preoperative chemotherapy could be used to predict patients at high risk of LR. This finding might be useful when considering surgical options to decrease the risk of LR.     

Management of Local Recurrence of Pediatric Osteosarcoma Following Limb-Sparing Surgery

Background

The optimal management of locally recurrent pediatric osteosarcoma is not established, especially after prior limb-sparing surgery. We describe our experience in the management of these patients and identify prognostic indicators of post-recurrence survival.

Methods

We conducted a retrospective, single-institution review of patients with locally recurrent osteosarcoma after limb-salvage surgery who were treated between October 1989 and January 2012. The management of each recurrence was evaluated, and patient, disease, and treatment factors were correlated with post-recurrence survival (PRS).

Results

Of 200 patients who underwent limb-sparing procedures, 18 (9 %) had biopsy-proven local recurrence. Recurrences occurred in soft tissue in 15 patients (83.3 %). Six patients (33.3 %) were amenable to repeat limb-sparing surgery. Median time to local recurrence was 1.4 (range 0.6–10.4) years. Median PRS was 11.8 months (range 3.7 months–12.1 years). Post-recurrence survival was significantly associated with the length of resection margins and was longer when recurrent tumors were resected with margins of ≥1 cm, compared with subcentimeter or positive margins (P = 0.03). Median PRS was longer in patients who underwent amputations (2.44 years) than those who underwent repeat limb-sparing surgery (0.86 years), and in patients who had distant metastases resected (2.7 years) than those who did not (0.85 years); however, differences were not significant.

Conclusions

Local management of recurrent osteosarcoma in a previously reconstructed limb is highly individualized. A sufficiently wide resection is important for local control of recurrences, independent of the type of surgery. Maintaining control of distant metastases may also contribute to improved survival.     

N-acethyl-cysteine reduces the occurrence of contrast-induced acute kidney injury in patients with renal dysfunction: a single-center randomized controlled trial

Background

The occurrence of contrast-induced acute kidney injury (CIAKI) has paralleled the increased number of diagnostic interventions requiring radiographic contrast media (CM). Several strategies aimed at preventing renal injury following iodine have been carried out over the last several years. The aim of this study was to evaluate the impact of three different strategies aimed at preventing CIAKI in patients with renal dysfunction (serum creatinine >1.25 mg/dl or estimated creatinine clearance <45 ml/min) receiving low osmolar CM for diagnostic–therapeutic procedures.

Methods

Candidates received 154 mmol NaHCO₃ solution (B0) at a rate of 3 ml/kg/h from at least 2 h before the procedure and at 1 ml/kg/h during and for the next 6–12 h; the same schedule plus N-acethyl-cysteine (NAC) 600 mg twice daily the day before and the day of the procedure (BN) or NAC as above plus 154 mmol NaCl solution at a rate of 3 ml/kg/h from at least 2 h before the procedure and at 1 ml/kg/h during and for the next 6–12 h (SN). Serum creatinine (SCr) was measured at baseline and on days 2 or occasionally 3 after CM. The main outcome measure was the occurrence of CIAKI, defined as a ≥25 % increase in SCr within 2–3 days of CM.

Results

The three groups were similar with regard to age, gender distribution, weight, baseline serum levels of creatinine, sodium, potassium, urate and estimated creatinine clearance. A larger proportion of individuals received ACEIs/ARAs in the BN group (p < 0.05), but in the SN group, more patients declared a past history of acute myocardial infarction or had high blood pressure, and few displayed mild–moderate left ventricular dysfunction (p < 0.05). CIAKI occurred in 24/123 (19.5 %) assessable patients (15/42 in the B0 group, 3/43 in the BN group and 6/38 in the SN group; p < 0.01). Thus, 15/42 patients who did not receive NAC developed CIAKI in contrast to 9/81 who did (p < 0.01). Multivariate logistic regression models showed that the use of NAC was the unique factor associated with a statistically significant influence for the occurrence of CIAKI (OR: 0.18; 95 % CI: 0.04–0.72; p = 0.016).

Conclusions

The results from this study show that: (1) the occurrence of CIAKI after low-osmolar CM administration is similar to that reported worldwide. (2) NAC-based renoprotective measures are superior for the prevention of CIAKI in patients with previous renal dysfunction. (3) They also demonstrate that bicarbonate expansion alone has limited value in preventing CIAKI. For those individuals at risk, combination prophylaxis including volume expansion plus NAC should be recommended to reduce the chance of overt kidney injury following CM administration.     

Changes in GIP gene expression following bariatric surgery

Background

After bariatric surgery, there is a significant improvement in type 2 diabetes (T2D). T2D has been linked to incretins, including glucose-dependent insulinotropic polypeptide (GIP). Analysis of bariatric surgery patients may help to understand the link between GIP and T2D.

Methods

Twenty-three morbidly obese patients underwent Roux-en-Y gastric bypass (RYGB) or gastric banding. Overall, there were 12 RYGB (5 T2D; 7 nondiabetic) patients and 11 gastric band (7 T2D; 4 nondiabetic) patients. Preoperative and postoperative blood samples were collected. Total RNA was extracted, cDNA synthesized, and real-time quantitative PCR were used to quantify gene expression. Student’s t test was used for statistical analysis.

Results

Postoperatively, T2D resolved or improved in 83.3 % (10/12) of the diabetic patients. Six (4 RYGB, 2 bands) patients discontinued hypoglycemic medications and four (3 RYGB, 1 band) patients discontinued the majority of their hypoglycemic agents. The remaining two diabetic patients (bands) showed no improvement. Postoperative GIP gene expression increased 4.36-fold (p = 0.02) in diabetic RYGB patients, whereas diabetic band patients increased 1.4-fold (p = 0.25). All diabetic patients with either resolution or improvement of T2D, had a 3.4-fold increase (p = 0.01) but nonresponders decreased 0.69-fold (p = 0.41). Nondiabetic RYGB patients increased 2.21-fold (p = 0.07) versus a 0.81-fold (p = 0.37) decrease of nondiabetic band patients.

Conclusions

This is one of the initial studies that show a significant increase in GIP gene expression following a RYGB. This increase correlates with the clinical resolution of T2D. The anatomical changes after RYGB may account for these changes. Based on this data, GIP may be a key peptide in the “foregut hypothesis” for resolution of T2D.     

The impact of recombinant parathyroid hormone on malignancies and mortality: 7 years of experience based on nationwide Danish registers

Summary

We used Danish registers to identify patients with osteoporosis, who had been treated with parathyroid hormone and evaluated the probability of developing cancer. We did not find an increased risk of cancer among the patients treated with parathyroid hormone.

Introduction

We evaluated the incidences of malignancies and mortality in osteoporotic patients treated with rPTH.

Methods

Using Danish nationwide registers, we identified patients diagnosed with osteoporosis in the period 1995 through 2010. Each patient treated with rPTH (“case”) was compared with 10 gender- and age-matched patients who did also have osteoporosis but did not receive rPTH (“control”).

Results

A total of 4,104 cases (80.3 % females) were identified. The mean age at the beginning of rPTH treatment was 70.9 (SD 9.7) years. During a follow-up time of 10,118 person-years for the cases and 88,005 person-years for the controls, a total of 255 cases (6.2 %) compared with 2,103 controls (5.1 %) experienced a cancer (Chi square, p?=?0.003). We found an adjusted cancer related HR of 1.1 (95 %CI 0.9–1.4) among the cases. Lung cancer was the only cancer type with a significantly increased rate among patients receiving rPTH (HR 1.7; 95 % CI 1.3–2.3). No cases developed osteosarcomas and nine controls developed osteosarcoma. During follow-up, 627 (15.3 %) cases died and 4,175 (10.2 %) controls died, which yielded an excess mortality risk of 26 % (95 % CI 16–37 %). This could be due to differences in the prevalence of vertebral fractures between the rPTH-treated and non-treated patients.

Conclusion

This study did not support the hypothesis describing a possible link between rPTH treatment and the development of cancer. We also conclude that osteosarcoma has not been diagnosed in any Danish patient receiving rPTH since the year 2003 when it was introduced on the market.     

Magnesium sulfate attenuates tourniquet pain in healthy volunteers

Purpose

Preoperative administration of an N-methyl-d-aspartate (NMDA) receptor antagonist has been shown to attenuate tourniquet-induced blood pressure increase under general anesthesia, suggesting that the mechanism of this blood pressure increase includes NMDA receptor activation. The attenuation of this increase may be associated with the pain relief induced by NMDA receptor antagonism. We tested the hypothesis that magnesium sulfate, an NMDA receptor antagonist, attenuates tourniquet pain.

Methods

Twenty-four healthy volunteers were randomly assigned to four groups (n = 6 each): control (normal saline), M1 (magnesium, 1 g), M2 (magnesium, 2 g), and M4 (magnesium, 4 g). Normal saline or magnesium solution was given intravenously over a 15-min period, in a double-blind fashion, before tourniquet inflation, which was continued for 60 min or until the “pain score” (0 = no pain, 100 = highest tolerable pain) reached 100. Pain scores were recorded before and every 5 min during tourniquet inflation. If subjects reported a pain score of 100 before the end of the 60-min period, we adopted a pain score of 100 for the remaining period.

Results

The duration of tourniquet inflation in the M4 group was significantly longer than that in the control group (54.3 ± 8.3 vs. 42.9 ± 9.9 min, P = 0.03). Pain scores in the M4 group were significantly lower than those in the control group from 10 through 50 min after the start of tourniquet inflation. The area under the curve for pain scores in the M4 group was significantly smaller than the areas in the other groups.

Conclusion

Magnesium sulfate, 4 g, significantly attenuated tourniquet pain in healthy awake volunteers, suggesting that NMDA receptor activation is involved in tourniquet pain.     

Effect of low-osmolar contrast medium iopromide and iso-osmolar iodixanol on DNA fragmentation in renal tubular cell culture

Background

Intravascular administration of iodinated contrast media continues to be a common cause of hospital-acquired acute kidney injury. Accumulating evidence suggests that radiocontrast agent-induced nephrotoxicity is associated with increased oxidative stress, which leads to renal tissue damage with DNA fragmentation. We therefore tested whether an iso-osmolar contrast medium (iodixanol) causes less oxidative DNA damage to renal tubular cells than a low-osmolar contrast medium (iopromide).

Methods

HK-2 cells (human proximal renal tubular cell line) were incubated at different time points (10 min–2 h) with increasing concentrations (20–120 mg/ml iodine) of iodixanol or of iopromide. Oxidative DNA damage to renal tubular cells was measured by alkaline comet assay (single-cell gel electrophoresis).

Results

Both iso- and low-osmolar contrast agents induced time- and concentration-dependent DNA fragmentation. DNA fragmentation was maximal at 2 h with 120 mg/ml iodine for iopromide (32 ± 27 tail moments) and iodixanol (46 ± 41 tail moments); both were significantly different from the control value with 3.15 ± 1.6 tail moments (Student’s t test; p < 0.001). After 1 and 2 h and for all concentrations, iodixanol produced significantly higher DNA fragmentation than iopromide (ANOVA for 1 h p = 0.039 and 2 h p = 0.025, respectively).

Conclusion

We were able to demonstrate for the first time that an iso-osmolar contrast medium induced even greater oxidative stress and DNA damage than a low-osmolar agent in HK-2 cells. This could provide an explanation for the nephrotoxicity that also is observed with iodixanol in clinical practice.     

Antinociceptive effect of intracerebroventricular administration of d-serine on formalin-induced pain

Purpose

In a previous study using the tail-flick test, we found that intracerebroventricular administration of d-serine, an endogenous co-agonist at the glycine sites of N-methyl-d-aspartate (NMDA) receptors, elicited an antinociceptive effect on thermal nociception. The purpose of the present study was to evaluate the effect of intracerebroventricular administration of d-serine on nociception induced by tissue damage or inflammation using the formalin test.

Methods

Infusion of drugs into the third ventricle in rat was performed via indwelling cannulae. Drugs were infused at a volume of 10 μl over 2 min, and the infusion cannula was left in place for 2 min before removal. The formalin test was performed 10 min after drug administration.

Results

Intracerebroventricular administration of d-serine significantly and dose-dependently decreased the number of flinches in both the early and late phases in the formalin test. This antinociceptive effect was antagonized by intracerebroventricular administration of L-701,324, a selective antagonist at the glycine sites of NMDA receptors.

Conclusion

The present data suggest that activation of NMDA receptors via glycine sites at the supraspinal level induces an antinociceptive effect on both acute and tonic pain.     

Beta-hemolytic streptococcal infections in trauma patients

Purpose

β-hemolytic streptococci (βHS) causes a diverse array of human infections. The molecular epidemiology of β-hemolytic streptococcal infections in trauma patients has not been studied. This study reports the molecular and clinical epidemiology of β-hemolytic streptococcal infections at a level 1 trauma centre of India.

Methods

A total of 117 isolates of βHS were recovered from clinical samples of trauma patients. The isolates were identified to species level and subjected to antimicrobial susceptibility testing. Polymerase chain reaction (PCR) assay was done to detect exotoxin virulence genes. The M protein gene (emm gene) types of GAS strains were ascertained by sequencing.

Results

Group A Streptococcus (GAS) was the most common isolate (64 %), followed by group G Streptococcus (23 %). A large proportion of GAS produced speB (99 %), smeZ (91 %), speF (95 %) and speG (87 %). smeZ was produced by 22 % of GGS. A total of 25 different emm types/subtypes were seen in GAS, with emm 11 being the most common. Resistance to tetracycline (69 %) and erythromycin (33 %) was commonly seen in GAS.

Conclusions

β-hemolytic streptococcal infections in Indian trauma patients are caused by GAS and non-GAS strains alike. A high diversity of emm types was seen in GAS isolates, with high macrolide and tetracycline resistance. SpeA was less commonly seen in Indian GAS isolates. There was no association between disease severity and exotoxin gene production.     

Platelet-rich plasma in patients with tibiofemoral cartilage degeneration

Introduction

Recently an articular cartilage repair has been given much attention in the orthopaedic field. Cartilage regeneration capacity is very limited. Optimal approach seems to be a delivery of natural growth factors. Autologous platelet-rich plasma (PRP) contains proliferative and chemoattractant growth factors. The objective of the present study was to determine if PRP can increase tibiofemoral cartilage regeneration and improve knee function.

Materials and methods

Fifty consecutive and strictly selected patients, affected by Grade II or III chondromalatia, underwent 1 year treatment (9 injections) with autologous PRP in a liquid form with 2.0 to 2.5-fold platelets concentration. Outcome measures included the Lysholm, Tegner, IKDC, and Cincinnati scores. Magnetic resonance imaging was used to evaluate cartilage thickness and degree of degeneration.

Results

The study demonstrated significant improvement in Lysholm (p < 0.05), Tegner (p < 0.05), IKDC (p < 0.05), and Cincinnati (p < 0.05) scores. Results improved at 12-month follow-up. Cartilage assessment revealed no significant cartilage regeneration (p < 0.05). There were no adverse events reported.

Conclusions

PRP significantly reduced pain and improved quality of live in patients with low degree of cartilage degeneration. Magnetic resonance imaging did not confirmed any significant cartilage condition improvement.     

Protective effect of beta-glucan on contrast induced-nephropathy and a comparison of beta-glucan with nebivolol and N-acetylcysteine in rats

Background

It has been shown that beta-glucan (BG), which has antioxidant and immunomodulatory effects, attenuats renal ischemia–reperfusion injury. We aimed to investigate whether BG might have a preventive role against the development of contrast-induced nephropathy and to compare its effect with nebivolol (Nb) and N-acetylcysteine (NAC).

Methods

Thirty-six Wistar albino female rats were randomly divided into six groups (n?=?6 each): control, contrast media (CM), BG, BG?+?CM, Nb?+?CM, and NAC?+?CM. With the exception of control and CM groups, the others were given drugs orally once a day for 5?days. Kidney function parameters, inflammatory parameters, and serum and renal tissue oxidative stress markers were measured.

Results

Increases of serum creatinine and blood urea nitrogen levels were significantly higher (p?p?p?p?Conclusion This study suggests that BG protects or ameliorates against contrast-induced nephropathy. Its beneficial effects may be similar to or greater than those of Nb or NAC.     

A switch from GnRH agonist to GnRH antagonist in castration-resistant prostate cancer patients leads to a low response rate on PSA

Purpose

At the time of castration resistance, it is recommended to realize hormonal manipulations before chemotherapy. We evaluated the impact of a switch from GnRH agonist to antagonist in patients with castration-resistant prostate cancer on PSA and testosterone levels at 3 months.

Methods

Retrospectively, 17 patients from 5 different centers undergoing androgen deprivation therapy and presenting rising PSA confirmed on 3 blood samples 2 weeks apart and despite a castrate testosterone level (<0.5 ng/ml) were reviewed. Antiandrogen withdrawal syndrome had been tested before the switch. Degarelix was administered as followed: 240 mg for the first injection and then 80 mg every month, subcutaneously. We evaluated the PSA and testosterone level variation 3 months after the switch. Patients who experienced a variation in PSA of less than 10% compared to the baseline or who had a more than 10% PSA decrease were defined as responders.

Results

Mean PSA level at the switch was 34.3 ± 50.3 ng/ml, with a mean testosterone level of 0.21 ± 0.13 ng/ml. Three months after the switch, mean PSA level was 59.9 ± 81.6 ng/ml (P = 0.061), with a mean testosterone level of 0.19 ± 0.08 ng/ml (P = 0.086). At 3 months, 4 patients (23%) responded to therapy. Thirteen patients (77%) experienced a rise in PSA of more than 10% compared to baseline; 41% of patients decreased their testosterone level. The limitations of this study are its retrospective nature and the limited number of patients.

Conclusion

Switch from an agonist to an antagonist of GnRH has a limited impact on PSA at 3 months in castration-resistant prostate cancer patients.