Pharmacokinetics and bioequivalence study of two ciprofloxacin hydrochloride tablets in healthy Chinese subjects under fasting and fed conditions: A randomized, open-label, two-formulation, two-sequence, two-period, single-dose crossover study.

OBJECTIVE: The study mainly aimed to determine the bioequivalence of two branded ciprofloxacin hydrochloride tablets (250 mg) under fasting and fed conditions. MATERIALS AND METHODS: The study was carried out in 48 healthy Chinese subjects under fasting and fed conditions with a randomized, open-label, two-formulation, two-sequence, two-period, single-dose crossover design. In each period of the study, the subjects were assigned to receive a single oral dose of 250 mg ciprofloxacin hydrochloride. Blood samples were collected from 1 hour before dosing to 36 hours after administration with 16 timepoints in total. The bioequivalence analysis was performed after ln-transformation of the ciprofloxacin pharmacokinetic parameters including Cmax, AUC0-t, and AUC0-∞. RESULTS: A total of 48 subjects were enrolled in the fasting and fed studies, and 1 of the subjects was excluded before drug administration. In the fasting study, the 90% CIs for the test/reference geometric mean ratios (GMRs) of the ln-transformed data for Cmax, AUC0-t, and AUC0-∞ were 85.41 - 100.97%, 95.40 - 100.27%, and 95.48 - 100.30%, respectively. For the fed study, the 90% CIs for the test/reference GMRs of the ln-transformed data for Cmax, AUC0-t, and AUC0-∞ were 90.15 - 113.75%, 99.10 - 103.77%, and 99.11 - 103.80%, respectively. These values all fell within the standard acceptance range of 80 - 125%. CONCLUSION: In the study, the generic (test) product of ciprofloxacin hydrochloride 250 mg was bioequivalent to the innovator (reference) product after single-, oral-dose administration under fasting and fed conditions.

Comprehensive Insights Into Renal Perivascular Epithelioid Cell Neoplasms: From Molecular Mechanisms to Clinical Practice.

Perivascular epithelioid cell neoplasms (PEComas) are a rare category of mesenchymal tissue tumors, manifesting across various tissues and organs such as the kidneys, liver, lungs, pancreas, uterus, ovaries, and gastrointestinal tract. They predominantly affect females more than males. PEComas characteristically express both melanocytic and smooth muscle markers, making immunohistochemistry vital for their diagnosis. Renal angiomyolipoma (AML) represents a common variant of PEComas, typically marked by favorable prognoses. Nonetheless, only a small fraction of subtypes, especially epithelioid AML, possess the capacity to be malignant. Renal PEComas usually appear as asymptomatic masses accompanied by vague imaging characteristics. The main methods for diagnosis are histopathological analysis and the application of immunohistochemical stains. Presently, a uniform treatment plan for renal PEComas is absent. Strategies for management include active surveillance, selective arterial embolization, surgical procedures, and drug-based treatments. The focus of this review is on renal PEComas, shedding light on their pathogenesis, pathological characteristics, clinical presentations, diagnosis, and treatment modalities, and incorporating a clinical case study.

Small-cell carcinoma of the prostate with negative CD56, NSE, Syn, and CgA indicators: A case report.

BACKGROUND: Small-cell carcinoma of the prostate (SCCP) is a clinically rare malignant tumor, accounting for < 1% of all prostate tumors. However, negativity for all SCCP neuroendocrine markers is rare. Herein, we report a case of SCCP with completely negative neuroendocrine markers and explore its clinicopathologic features, thus improving the understanding of its clinical diagnosis and management. CASE SUMMARY: We report the case of a 48-year-old patient with SCCP negative for common sensitive neuroendocrine-staining indicators. Dysuria was the first symptom, and rectal examination revealed a hard prostate, palpable nodules, diffuse prostate enlargement, no pressure pain, no blood staining in the finger sleeve, 1.33 ng/mL total prostate-specific antigen level, and a free-to-total prostate-specific antigen ratio of 0.21 ng/mL. Ultrasound suggested a prostate size of 5.3 cm × 5.8 cm × 5.6 cm, and magnetic resonance imaging suggested prostate cancer. The lower posterior bladder wall, rectal mesentery, and bilateral seminal vesicles were invaded, with multiple lymph node metastases in the pelvis. A whole-body bone scan suggested an abnormally active multiple bone metabolism and possible bone metastases. Head and lungs computed tomography revealed no significant nodal shadow. Following a pathological diagnosis of SCCP after a prostate puncture, with negative indicators of common sensitive neuroendocrine staining, chemotherapy was administered; the patient died 4-5 mo after SCCP diagnosis. CONCLUSION: SCCP is a rare disease characterized by atypical clinical symptoms, limited treatment options, a short survival period, and a poor prognosis.

Primary adrenal diffuse large B-cell lymphoma with normal adrenal cortex function: A case report.

BACKGROUND: Diffuse large B-cell lymphoma, which accounts for about approximately 30% to 40% of non-Hodgkin's lymphomas, is the most common type and is a class of aggressive B-cell lymphomas. However, diffuse large B-cell lymphomas primary to the adrenal gland are rare. CASE SUMMARY: A 73-year-old man was admitted with abdominal pain and fatigue. After admission, enhanced adrenal computed tomography indicated irregular masses on both adrenal glands, with the larger one on the left side, approximately 8.0 cm × 4.3 cm in size. The boundary was irregular, and surrounding tissues were compressed. No obvious enhancement was observed in the arterial phase. Resection of the left adrenal gland was performed. Pathological diagnosis revealed diffuse large B-cell lymphoma. After surgery, the patient received R-CHOP immunochemotherapy. During the fourth immunochemotherapy, patient condition deteriorated, and he eventually died of respiratory failure. CONCLUSION: R-CHOP is the conventional immunochemotherapy for primary adrenal diffuse large B-cell lymphoma. Surgery is mainly used to diagnose the disease. Hence, the ideal treatment plan remains to be confirmed.

Pharmacokinetics and Bioequivalence of Two Formulations of Rosuvastatin Following Single-dose Administration in Healthy Chinese Subjects Under Fasted and Fed Conditions.

The main objective of the study was to evaluate the bioequivalence of two rosuvastatin calcium tablets in healthy Chinese subjects under fasted and fed conditions. The study was carried out using a randomized, open-label, two-formulation, two-sequence, two-period, single-dose crossover design, with a washout period of 7 days. Both the fasted study and fed study enrolled 28 subjects. In each study period, the subjects were administrated a single oral dose of the test product or reference product of rosuvastatin 10 mg. Blood samples were collected from pre-dose to 72 hours after administration with 16 time points in total. Bioequivalence evaluation was performed using ln-transformed pharmacokinetic parameters of rosuvastatin, including Cmax , AUC0-t , and AUC0-∞ . In the present study, 95% confidence intervals (CIs) of test/reference geometric mean ratios (GMRs) of Cmax , AUC0-t , and AUC0-∞ under the fasted and fed conditions were all within the acceptance range of 80%-125%. Additionally, only one subject experienced one adverse event (AE). High-fat meals reduced the Cmax , AUC0-t , and AUC0-∞ , but had no significant effects on the λz, t1/2 , or Tmax of rosuvastatin. In the current study, the test product was bioequivalent to the reference product, and a single dose of rosuvastatin (10 mg) was well-tolerated. Food decreased the systemic exposure of rosuvastatin without the effects on the Tmax or elimination rate.

Verapamil inhibits ureteral scar formation by regulating CaMK II-mediated Smad pathway.

Verapamil is reported to prevent scar formation. However, whether verapamil is involved in the ureteral stricture scar and the underlying mechanism need further investigation. Fibroblasts were isolated from ureteral scar tissues. TGF-ß1 stimulation was used to induce fibrosis of fibroblasts. Inhibition of CaMK II was achieved by shRNA transfection. CCK-8 was performed to evaluate cell viability. qRT-PCR was applied to determine the level of mRNA while western blotting was used to determine the level of proteins. Immunofluorescence was used to detect the level of vimentin, collagen I and collagen III. Primary fibroblasts was successfully isolated from ureteral scar tissues. TGF-ß1 stimulation was capable to induce collagen production and fibrosis in primary fibroblasts while inhibition of CaMK II attenuate collagen production. Overexpression of wild type CaMK II lead to further increase of collagen production upon TGF-ß1 stimulation while the mutated CaMK II did not exert this promotion. Treatment of verapamil inhibits TGF-ß1 induced collagen production via inhibiting CaMK II. In present study, we revealed a vital role of Verapamil and CaMK II in the formation of ureteral scar. Verapamil inhibited TGF-ß1 induced collagen fiber formation by regulating CaMK II. Our finding might provide new insight into mechanism of prevention and treatment of ureteral scar.

[Update of combined therapies with docetaxel for hormone-independent prostate cancer].

Hormone-independent prostate cancer (HIPC) is the end stage of prostate cancer, with a short median survival of 9-18 months for the patients. Two large phase III studies have demonstrated a survival advantage of docetaxel chemotherapy in HIPC patients. New combined protocols have been developed with promising results. These protocols propose a combination with docetaxel, chemotherapy, antiangiogenic agents, vaccine and biological drugs. This review focuses the progress achieved the combined therapies for HIPC.

[Characterization of a novel transplantable orthotopic nude mouse model with xenografted human bladder transitional cell tumor (BIU-87)].

OBJECTIVE: A mouse model of orthotopic bladder cancer simulating its human counterpart is of great importance in preclinical evaluation of new treatment modalities such as immunotxin therapy. The aim of the present study is to establish a novel nude mouse model with xenografted human bladder cancer. METHODS: Single cell suspension of an established human bladder transitional cell carcinoma (TCC) cell line BIU-87 was instilled into nude mouse bladders which were pretreated with mild acid washing. The tumor growth in mouse bladder was assessed weekly by magnetic resonance imaging (MRI). At intervals following implantation and MRI tumor detection, the animals were sacrificed for necropsy, histological examination and immunocytochemical studies. RESULTS: The overall tumor establishment was 92.9% (52/56 mice) at 7 - 36 days, while in the subgroup of animals sacrificed at 12 - 13 days, 40 out of 42 animals (95.2%) developed TCC, the majority of which was superficial. The tumor stages were assessed by gross and histopathology. Histological examination confirmed the presence of grade II - III TCC. Immunocytochemistry confirmed that the tumor model maintained the biological and immunological features of BIU-87 cells. The changes seen on MRI images well correlated with the extent of tumor invasion identified by histology. Carcinoma in situ could be detected histologically at 7 - 9 days post-inoculation and progressed into papillary or invasive tumors thereafter. CONCLUSION: The orthotopic BIU-87 TCC model in nude mice is highly reproducible and is ideal for preclinical studies on experimental intravesical therapies.

[Preparation of lung targeting azithromycin liposomes and its tissue distribution in mice].

AIM: To prepare lung targeting azithromycin cationic liposomes and to observe its tissue distribution in mice. METHODS: The azithromycin cationic liposomes were prepared by thin film method with freeze-thawing steps. HPLC method was established and validated for the determination of azithromycin in tissues of mice. RESULTS: The particle size of the liposomes was 6.582 microm with zeta potential of +19.5 mV. The entrapment efficiency was more than 75%. The liposomes was stable in 6 months stored at 4 degrees C. The release in vitro was characterized by Higuchi equation. Azithromycin liposomes and free azithromycin solution were injected intravenously at a dose of 80 mg x kg(-1) to mice. Compared with solution, liposomes were characterized by slower clearance, increased half-life and the AUC increased by 7.4 fold in lung. CONCLUSION: Thin film method with freeze-thawing steps could increase the entrapment efficiency and increase the particle size of azithromycin liposomes. After modification of lipid membrane with stearylamine, the cationic liposomes were prepared. The azithromycin concentration and AUC increased in lung after iv administration to mice of the cationic liposomes. This offered a good information for preparing liposomes targeting on the lung.

Influence of mesenchymal stem cells on expression of AQP1 and AQP2 in rats with nephropathy induced by adriamycin.

This study aims to explore the therapeutic effect of bone marrow mesenchymal stem cells on adriamycin nephrosis, and the potential mechanism. The rat experimental nephropathy model was established by unilateral nephrectomy combined repeated injecting adriamycin (ADR). Thirty adriamycin nephrosis rats were randomly divided into three groups, including ADR (n=10), MSCs transplantation through peripheral veins groups (M-V, n=10), and MSCs transplantation through right renal artery groups (M-A, n=10), and there was another normal control group (N, n=10). This study lasted 8 weeks, 24 hours urine was collected through simple metabolic cage to measure urinary volume and urine protein quantitation in 24 hours. The levels of plasma albumin (ALB), sodium were measured by biochemical analysis. The expressions of AQP1-2 were measured by immuno-histochemistry assay. Kidney medulla ultramicroscopic structure was observed by TEM. The results indicated that the ALB and 24 h urinary volume have significant increased in M-V and M-A group compared to the ADR group (P<0.05). Furthermore, the serum sodium and urine protein quantitation in 24 hours were decreased in M-V and M-A group compared to ADR group (P<0.05). Protein expression of AQP1-2 had been remarkably decreased (P<0.05). It showed degenerative changes of kidney ultra microscopic structures of the ADR rats, while MSCs transplantation could significantly improve the damage. In conclusion, in adriamycin nephropathy rats, MSCs transplantation exerts its therapeutic effects by decrease urinary albumin excretion, increase ALB, decrease sodium and the expression of AQP1-2 in renal tubules.

Breastfeeding and maternal hypertension and diabetes: a population-based cross-sectional study.

OBJECTIVE: This study aimed to assess the association of breastfeeding and maternal hypertension and diabetes in Beijing, China. SUBJECTS AND METHODS: A cross-sectional study was conducted in four urban communities of Beijing, China, with 9,128 parous women 40-81 years of age who had had only one lifetime birth. Each participant completed a detailed survey and accepted blood pressure measurement and blood glucose testing. Moreover, self-reported hypertension and diabetes were confirmed by review of medical records. RESULTS: After the analysis was adjusted for the potential confounders, including age, body mass index (BMI), waist to hip ratio (WHR), working status, educational level, drinking, smoking, family history of hypertension, age of menarche, menopause, oral contraceptive use, age of child-bearing, and postpartum BMI, the odd ratio (OR) of hypertension was 1.18 (95% confidence interval [CI], 1.05-1.32) for women who did not breastfeed, compared with women who did. In addition, the ORs for >0 to 6 months, >6 to 12 months, and >12 months of breastfeeding were 0.87 (95% CI, 0.76-0.99), 0.83 (95% CI, 0.68-1.00), and 0.79 (95% CI, 0.65-0.97), respectively, compared with women who did not breastfeed. With adjustment for age, WHR, working status, educational level, family history of diabetes, and postpartum BMI, women who did not breastfeed increased the risk of diabetes (OR=1.30; 95% CI, 1.11-1.53) compared with women who did. Moreover, women who breastfed for >0 to 6 months (OR=0.81; 95% CI, 0.67-0.98) and >6 to 12 months (OR=0.46; 95% CI, 0.26-0.84) had a lower risk of diabetes, compared with women who did not breastfeed. CONCLUSIONS: Chinese mothers who did not breastfeed were more likely to develop hypertension and diabetes in later life.

Research progress in potential urinary markers for the early detection, diagnosis and follow-up of human bladder cancer.

OBJECTIVE: To summarize and evaluate various urinary markers for early detection, diagnosis and follow-up of human bladder cancer. METHODS: A MEDLINE and PUBMED search of the latest literature on urinary markers for bladder cancer was performed. We reviewed these published reports and made a critical analysis. RESULTS: Most urinary markers tend to be less specific than cytology, yielding more false-positive results, but demonstrating an advantage in terms of sensitivity, especially for detecting low grade, superficial tumors. Some tumor markers appear to be good candidates for early detection, diagnosis, and follow-up of human bladder cancer. CONCLUSION: A number of urinary markers are currently available that appear to be a applicable for clinical detection, diagnosis, and follow-up of bladder cancer. However, further studies are required to determine their accuracy and widespread applicability.

Apoptin induces apoptosis in human bladder cancer EJ and BIU-87 cells.

OBJECTIVE: To investigate whether apoptin is a apoptosis-inducing protein with a potential for bladder cancer therapy. METHODS: We constructed a PCDNA3/Apoptin eukaryotic expression vector, and transfected this vector into bladder cancer cell lines BIU-87 and EJ, then observed the results by RT-PCR, transmission electron microscopy, MTT assay and the flow cytometry (TUNEL method). RESULTS: PCDNA3/Apoptin successfully induced a high level apoptosis in both bladder cancer cell lines, compared with the controls (p<0.05). CONCLUSIONS: Apoptin can induce high level apoptosis in human bladder cancer EJ and BIU-87 cells, which suggests a potential for human bladder cancer therapy.

ppGalNAc T1 as a potential novel marker for human bladder cancer.

OBJECTIVES: To investigate the effect of glycopeptide-preferring polypeptide GalNAc transferase 1 (ppGalNAc T1) targeted RNA interference (RNAi) on the growth and migration of human bladder carcinoma EJ cells in vitro and in vivo. METHODS: DNA microarray assays were performed to determine ppGalNAc Ts(ppGalNAc T1-9) expression in human bladder cancer and normal bladder tissues. We transfected the EJ bladder cancer cell line with well-designed ppGalNAc T1 siRNA. Boyden chamber and Wound healing assays were used to investigate changes of shppGalNAc T1-EJ cell migration. Proliferation of shppGalNAc T1-EJ cells in vitro was assessed using [3H]-thymidine incorporation assay and soft agar colony formation assays. Subcutaneous bladder tumors in BALB/c nude mice were induced by inoculation of shppGalNAc T1-EJ cells and after inoculation diameters of tumors were measured every 5 days to determine gross tumor volumes. RESULTS: ppGalNAc T1 mRNA in bladder cancer tissues was 11.2-fold higher than in normal bladder tissues. When ppGalNAc T1 expression in EJ cells was knocked down through transfection by pSUPER-shppGalNAc T1 vector, markedly reduced incorporation of [3H]-thymidine into DNA of EJ cells was observed at all time points compared with the empty vector transfected control cells. However, ppGalNAc T1 knockdown did not significantly inhibited cell migration (only 12.3%). Silenced ppGalNAc T1 expression significantly inhibited subcutaneous tumor growth compared with the control groups injected with empty vector transfected control cells. At the end of observation course (40 days), the inhibitory rate of cancerous growth for ppGalNAc T1 knockdown was 52.5%. CONCLUSION: ppGalNAc T1 might be a potential novel marker for human bladder cancer. Although ppGalNAc T1 knockdown caused no remarkable change in cell migration, silenced expression significantly inhibited proliferation and tumor growth of the bladder cancer EJ cell line.