Effect of probiotics on the maintenance of intestinal homeostasis after chemotherapy: systematic review and meta-analysis of pre-clinical studies.

Gastrointestinal mucositis (GIM) is an inflammation caused by antitumor therapy, especially after chemotherapy and radiotherapy. Currently in the clinical practice, only palliative measures are taken to treat GIM, representing the main clinical limitation in the management of this condition. Several studies have highlighted the potential benefits of probiotics for the management of GIM, but the actual role of these microorganisms in the maintenance of intestinal homeostasis remains elusive. In this context, here we aimed to realise a systematic review with meta-analysis to evaluate the effect of probiotics on experimental GIM. The meta-analysis showed that probiotics significantly suppressed the body weight loss related to GIM in rodents (95% confidence interval (CI): -2.67 to -0.70; I2=98%, P<0.00). Subgroup analysis showed that pre-treatment (≥7 days before chemotherapy) (95% CI: -8.84 to -0.17; I2=98%, P<0.04) with a high dose of probiotics (≥ 109 cfu/day) (95% CI: -2.58 to -0.28; I2=98%, P<0.00) comprising two or more microorganism species (95% CI: -6.49 to -0.28; I2=96%, P=0.03) remedied GIM more effectively. It was also revealed that fungi (specifically Saccharomyces boullardii) are more effective in remedying GIM than bacteria (P=0.03 vs P<0.00), and the mouse models are more receptive than rats to the enteroprotective effects of probiotics (95% CI: -4.76, -0.69; I2=97%, P=0.01). Qualitative analyses highlighted that probiotics suppress GIM through several mechanisms; they reduce the intestinal permeability, suppress the pro-inflammatory cytokine production while stimulating production and secretion of anti-inflammatory cytokines, inhibit the signalling pathways coupled to inflammation and apoptosis, accelerate the proliferation of enterocytes, reduce the levels of reactive oxygen species, and help maintain the protective mucus layer. In conclusion, this review highlights the therapeutic benefits of probiotics in experimental GIM.

Development of torsade de pointes caused by exacerbation of QT prolongation during clipping of cerebral artery aneurysm in a patient with subarachnoid haemorrhage.

We report the case of a 79-yr-old woman with subarachnoid haemorrhage (SAH) in whom torsade de pointes (TdP) caused by worsening the QT prolongation occurred during clipping of cerebral artery aneurysm. This patient shows a potential risk of occurrence of life-threatening tachyarrhythmia, TdP by prolonging the QT interval during surgery in patients with SAH even with no additional factors that predispose to TdP. Therefore, a proper monitoring of the QT interval is necessary as a predictor of TdP. When ventricular tachyarrhythmia occurs, recognition of TdP is important because antiarrhythmic drug therapy for TdP is different from that for ventricular tachyarrhythmias that is not TdP.

Positive pressure ventilation during fibreoptic intubation: comparison of the laryngeal mask airway, intubating laryngeal mask and endoscopy mask techniques.

BACKGROUND: The efficacy of delivery of mechanical ventilation through different airway devices during fibreoptic intubation is not known. METHODS: We compared the laryngeal mask airway (LMA), intubating laryngeal mask (ILM) and endoscopy mask for positive pressure ventilation (PPV) during fibreoptic intubation. In 80 adult paralysed patients, fibreoptic intubation was performed during PPV using a combination of a size 3 or 4 LMA with a 6.0 mm nasal RAE tracheal tube (LMA3/4 group; n=22), a size 5 LMA with a 7.0 mm nasal RAE tube (LMA5 group; n=18), an ILM with an 8.0 mm special reinforced tracheal tube (ILM group; n=20) or an endoscopy mask (Patil mask) with a 7.5 mm standard tracheal tube (Patil group; n=20). The inspiratory and expiratory tidal volumes (VI and VE) with a ventilation pressure of 20 cm H2O were measured using a pneumotachograph. RESULTS: Mean VE values during fibreoptic intubation in the LMA5 [5.3 (SD 1.5) ml kg(-1)] and ILM [7.1 (2.3) ml kg(-1)] groups were greater than in the LMA3/4 group [2.6 (1.0) ml kg(-1), P<0.0001]. The mean VE was greater in the Patil group [20.6 (4.9) ml kg(-1)] than in the other three groups (P<0.0001). Gastric insufflation during intubation was more frequent in the Patil group (30%) than in the other three groups (4.5-5.6%) (P<0.05). CONCLUSION: PPV is possible with the LMA, ILM or endoscopy mask during fibreoptic intubation. With an airway pressure of 20 cm H2O, ventilation during intubation using a size 3 or 4 LMA was almost insufficient, while ventilation using a size 5 LMA or an ILM was almost acceptable. Ventilation during intubation with the endoscopy mask was greater than that with the LMA or ILM, but gastric insufflation was more frequent.

Apoptotic cell death and Smad4 expression in transitional cell carcinoma of the renal pelvis and ureter.

PURPOSE: To investigate the frequency of apoptosis and the expression of Smad4 protein as well as their roles in transitional cell carcinoma (TCC) of the renal pelvis and ureter. METHODS: Apoptosis was detected by using terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) technique in 34 formalin-fixed and paraffin-embedded specimens of renal pelvic and ureteral TCC. The expression of Smad4 was immunohistochemically studied. RESULTS: The incidence of apoptosis ranged from 1.10 to 3.75% with a median of 2.50% in TCC of the renal pelvis and ureter. The incidence of apoptosis was noted to be closely related to histologic grade but not to pathologic stage of the cancer. The expression of Smad4 was detected in six of 34 cases (17.6%). Regarding subcellular distribution, Smad4 protein was localized both in cytoplasm and nucleus of the cancer cells. In comparing the incidence of apoptosis with the expression of Smad4, no significant associations were seen between them. The expression of Smad4 was not related to the tumor grade nor stage of the cancer. CONCLUSIONS: The present study demonstrated close association of the incidence of apoptosis with the tumor grade of TCC of the renal pelvis and ureter. Significance of Smad4 expression was not noted in the study. It suggests that apoptotic cell death may play an important role in the tumor progression of renal pelvic and ureteral TCC.

Evaluation of cell proliferation, apoptosis, and angiogenesis in transitional cell carcinoma of the renal pelvis and ureter.

OBJECTIVES: To investigate cell proliferation, apoptosis, and angiogenesis and their roles in transitional cell carcinoma (TCC) of the renal pelvis and ureter. METHODS: Formalin-fixed and paraffin-embedded tissue blocks from 42 patients with TCC of the renal pelvis and ureter were studied. Cell proliferation was assessed by Ki-67 immunostaining, and the proliferation index (PI) was expressed as a percentage of Ki-67-positive cells. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), and the apoptotic index (AI) was expressed as a percentage of TUNEL positive cells. Angiogenesis was evaluated by CD31 immunostaining, and microvessel density (MVD) was expressed as the average of the microvessel count. RESULTS: The PI ranged from 5.9% to 48.0% (median 20.03%), AI from 1.0% to 4.2% (median 2.26%), and MVD from 16.0 to 146.0 (median 56.88) in TCC of the renal pelvis and ureter. Statistical analysis revealed close associations of both PI and MVD with tumor stage and of AI with tumor grade. Our study demonstrated a strong relationship between PI and MVD, but did not show associations of AI with PI or MVD in TCC of the renal pelvis and ureter. CONCLUSIONS: It is suggested that the high activity of tumor cell proliferation with rich neovascularization may be related to the high malignant potential of the cancer, and evaluation of cell proliferation combined with angiogenesis may be useful in predicting the progression of the renal pelvic and ureteral TCC.

[Metastatic liver tumor arising from prostate cancer following transurethral resection of the prostate--a report of two cases].

We herein present a report of metastatic liver tumor arising from prostate cancer following transurethral resection of the prostate (TUR) in two patients. The two patients were diagnosed as having moderately differentiated prostate adenocarcinoma, either stage C or B2, and underwent hormonal and/or radiation therapy. TUR was performed due to the patients' complaints of urinary outlet obstruction. Liver metastasis, without evidence of bone or pulmonary metastasis, was then noted 23 and 5 months later in the patients with stage C and B2 prostate cancer, respectively. It is possible that the process of TUR is related to the release of tumor cells from the prostate into the systemic circulation and involved in the development of liver metastasis.

Cisplatin-induced germ cell apoptosis in mouse testes.

The purpose of this study was to investigate whether exposure of male mice to cisplatin induces apoptosis in male germ cells and the possible role of apoptosis in cisplatin-induced testicular damage. Forty-eight male BALB/c mice were divided into cisplatin and control groups. The mice from the cisplatin group received a single intraperitoneal injection of cisplatin of either 1, 5, or 10 mg/kg. The control group received a single intraperitoneal injection of saline alone. The testes were removed on days 1, 3, and 7 after cisplatin administration, respectively. Following histological examination, apoptotic indices (AIs) were measured within seminiferous tubules of the mouse testes by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. A low incidence of spontaneous apoptosis was observed in controls, particularly in spermatogonia and spermatocytes of the mouse testes. After cisplatin administration, both increased Als and decreased spermatozoa and spermatids were found in the seminiferous tubules of the mouse testes. Cisplatin-induced apoptosis was found in spermatogonia, spermatocytes, and spermatids of the mouse testes. In comparison to the control values, AIs increased 2.6- to 6.8-fold in cisplatin-treated mouse testes. AIs reached the highest level on day 1 following 1 mg/ kg, on day 3 following 5 mg/kg, and on day 7 following treatment of 10 mg/kg cisplatin. The study showed that cisplatin-induced germ cell apoptosis in the mouse testes was related to both the dose response and the time course of response. It is suggested that cisplatin-induced germ cell apoptosis may result in decreased spermatogenesis, and the higher dose of cisplatin may delay the occurrence of apoptosis in the mouse testes.

Galvanotactic response of mouse epididymal sperm: in vitro effects of zinc and diethyldithiocarbamate.

This study was conducted to evaluate the galvanotactic response of mouse epididymal sperm as well as the in vitro effects of Zn-acetate and diethyldithiocarbamate (DEDTC) on the galvanotaxis of sperm. The galvanotaxis of sperm was observed in a direct current (DC) electric field between 0 and 10 V/cm. The sperm were treated with Zn-acetate or DEDTC at concentrations of 0.02, 0.20, and 2.00 mM before the observations. The sperm exhibited galvanotaxis toward both cathode and anode in the fields between 1 and 9 V/cm. The number of sperm that accumulated at both electrodes was found to reach the highest level between 5 and 7 V/cm. In comparison with the results from untreated sperm, the number of accumulated sperm at the electrodes increased with the addition of 0.20 and 2.00 mM Zn-acetate, but decreased with the addition of DEDTC at all 3 concentrations. The galvanotaxis of mouse epididymal sperm is related to the field strengths, and the guidance of sperm migration may be influenced by the sex chromosomes. The galvanotaxis of the sperm may be improved by addition of Zn-acetate but depressed by DEDTC in the presence of DC electric fields.

Cell proliferation and apoptosis with BCL-2 expression in renal cell carcinoma.

OBJECTIVES: To investigate cell proliferation, apoptosis, and bcl-2 immunoreactivity in renal cell carcinoma (RCC). METHODS: Formalin-fixed and paraffin-embedded tissue blocks from 70 patients with RCC were studied. Cell proliferation activity was detected by Ki-67 immunostaining and the proliferation index (PI) was expressed as a percentage of the Ki-67-positive cells in the tumor cells. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), and the apoptotic index (AI) was expressed as a percentage of the TUNEL-positive cells in the tumor cells. Immunoreactivity of bcl-2 was assessed immunohistochemically and coexpression of Ki-67 with bcl-2 was examined by double immunostaining. RESULTS: The PI ranged from 5.0% to 44.0% (median 19.23%) and the AI from 0.9% to 3.4% (median 2.13%) in RCC. Statistical analysis revealed close associations between PI and tumor grade and stage, and a significant relationship between AI and the tumor grade of RCC. The expression of bcl-2 was detected in 24 (34.3%) of 70 RCCs. Coexpression of Ki-67 with bcl-2 was noted in 3 of the 24 RCCs with bcl-2 expression. The expression of bcl-2 was not related to PI, AI, or the clinicopathologic factors of RCC. CONCLUSIONS: Our observations suggest that active cell proliferation may be accompanied by frequent apoptosis and that cell proliferation as reflected by Ki-67 staining may be the most important parameter of cell turnover in RCC.

[Anesthetic management for an adult patient with secundum atrial septal defect associated with a large left-to-right shunt].

We describe the case of a 68-year-old woman with secundum atrial septal defect associated with a large left-to-right shunt and congestive heart failure. The patient with a pancreatic tumor was scheduled for hepatic cholangiojejunostomy and cholecystectomy. To determine the ratio of pulmonary to systemic flow (Qp/Qs) as an indicator for the magnitude of left-to-right shunt, oxymetric catheters were placed in the superior vena cava and pulmonary artery. In addition, oxygen delivery was assessed using superior vena cava oxygen saturation (SsvcO2). Although the patient was anesthetized with high-dose fentanyl to supplement nitrousoxide and sevoflurane, the Qp/Qs markedly increased after skin incision. Epidural local anesthetic was then administered. The Qp/Qs decreased to the preoperative value and the hemodynamic condition was improved thereafter. The operative course was uneventful. This case illustrates the potential usefulness of continuous measurement of the Qp/Qs and SsvcO2 for anesthetic management of adult patients with secundum atrial septal defect.