Preparation of 5-aryl-3-alkylthio-l,2,4-triazoles and corresponding sulfones with antiinflammatory-analgesic activity

In this study, a series of 5-aryl-3-alkylthio-1,2,4-triazoles and corresponding sulfones were prepared with the objective of developing better analgesic-antiinflammatory compounds with minimum ulcerogenic risk. The structures of the compounds were elucidated by spectral and elemental analysis. The compounds were assayed per os in mice for their antiinflammatory and analgesic activity as well as the ulcerogenic risk and acute toxicity. Several of these compounds showed significant activity. Alkylsulfone derivatives were found to be much more potent analgesic-antiinflammatory agents than the corresponding alkylthio analogs. Compounds 9 and 11 were the most active of the series in both analgesic and antiinflammatory activity tests. In contrast to reference compound acetyl salicylic acid, these compounds did not induce gastric lesions in the stomach of experimental animals at the doses that exhibited analgesic/antiinflammatory activity.     

Detection of parathyroid hormone using an electrochemical impedance biosensor based on PAMAM dendrimers

This paper presents a novel hormone‐based impedimetric biosensor to determine parathyroid hormone (PTH) level in serum for diagnosis and monitoring treatment of hyperparathyroidism, hypoparathyroidism and thyroid cancer. The interaction between PTH and the biosensor was investigated by an electrochemical method. The biosensor was based on the gold electrode modified by 12‐mercapto dodecanoic (12MDDA). Antiparathyroid hormone (anti‐PTH) was covalently immobilized on to poly amidoamine dendrimer (PAMAM) which was bound to a 1‐ethyl‐3‐(3‐dimethylaminopropyl)‐carbodiimide/N‐hydroxysuccinimide (EDC/NHS) couple, self‐assembled monolayer structure from one of the other NH₂ sites. The immobilization of anti‐PTH was monitored by electrochemical impedance spectroscopy, cyclic voltammetry and scanning electron microscope techniques. After the optimization studies of immobilization materials such as 12MDDA, EDC–NHS, PAMAM, and glutaraldehyde, the performance of the biosensor was investigated in terms of linearity, sensitivity, repeatability, and reproducibility. PTH was detected within a linear range of 10–60 fg/mL. Finally the described biosensor was used to monitor PTH levels in artificial serum samples. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:815–822, 2015     

A comparison of the effect of long-term starvation on responses to low-temperature stress by juvenile rainbow (Oncorhynchus mykiss) and brown (Salmo trutta) trout reveal different responses in the two species

Biometric parameters and oxidative stress indicators were measured in liver and muscle samples from rainbow trout and brown trout juveniles exposed to a 45-day starvation period at low water temperature. As a general tendency, hepatic antioxidant enzyme activities in both species increased with fasting to eliminate the harmful effects of reactive oxygen species (ROS). However, the metabolic response to food deprivation in the muscle of each species was different. Lipid peroxidation levels in both species increased with starvation. We concluded that (1) low water temperature enhances ROS production in salmonids because of increased polyunsaturated fatty acid content in the cell membrane; (2) starvation significantly impaired the growth parameters of brown trout, yet the reverse was found for rainbow trout; and (3) despite this negative interaction, brown trout juveniles can physiologically tolerate oxidative stress caused by starvation and can therefore be cultivated under stressful conditions even in their early life stages.     

Cadmium-induced changes in epithelial cells of the rat stomach

The aim of this study was to determine the changes in the function and fine structure of the gastric mucosa following exposure to high cadmium (Cd) for 30 d in rats. In the present study, control antimals were fed with normal food and tap water and the remaining animals received Cd (15 ppm CdCl₂) in drinking water for the same period. Receiving Cd for 30 d increased the mean blood (p<0.01) and mucosa (p<0.001) Cd levels, while decreased mucus thickness, mucin content (p<0.01) significantly. Basal acid output fell significantly (p<0.01). Light and electron microscopic examination revealed the following: (1) Cd decreases the mean number of surface mucous, isthmic-neck, parietal cells (p<0.05) and chief cells (p<0.001) per unit from the control value and (2) in some cells of zymogenic unit, the Cd-induced alterations were characterized with dilated Golgi cisternae, focal enlarged endoplasmic reticulum, broken tubulovesicles, degenerated mitochondria, dense nuclei, as well as lysosomal structures. We concluded that Cd augments the elimination rate of zymogenic unit’s cells by increasing the alteration rate, and the reduced basal acid output, mucin content, and mucus thickness can be explained easily with the loss of zymogenic unit’s cell population.     

Cadmium-induced changes in parietal cell structure and functions of rats

The aim of this study was to determine the cadmium (Cd)-induced functional and structural changes in gastric parietal cells of male rats exposed to high Cd for 30 d. In the present study, control animals were fed with normal food and tap water; the remaining animals received Cd (15 ppm CdCl₂) in drinking water for the same period. Receiving Cd for 30 d increased the mean blood Cd level, the mean tissue Cd content, and the mean blood pressure (p<0.01, p<0.001, p<0.01, respectively). The basal acid output fell; however, the increases in stimulated acid output were not statistically significant. Light and electron microscopic examination revealed respectively that (1) Cd decreases the mean parietal cell number per unit from the control value of 23.46±3.84 to 19.46±2.12 (p<0.05) and it affected preferentially the cells located at the distal half of the zymogenic unit and (2) in parietal cells, the Cd-induced alterations were characterized with swollen canalicular profiles, broken-down tubulovesicles, or degenerated mitochondria. We concluded that Cd augments the elimination rate of parietal cells by increasing the alteration rate and reduced basal acid output can be explained easily with the loss of parietal cell population.     

SAHA induce hippo pathway in CCA cells without increasing cell proliferation

Background

Cholangiocarcinoma is a malignant tumor originating from bile duct epithelial cells. Since tumor metastasis is associated with poor prognosis and short-term survival of patients, there is an urgent need for alternative therapeutic approaches for CCA. Because of that reason, we aimed to investigate effect of SAHA which is known as HDAC inhibitor on extrahepatic cholangiocarcinoma cell line (TFK-1).

Methods

Cell cycle was measured by Muse Cell Analyzer. YAP, TAZ, TGF-β protein levels were determined by western-blotting method. TEAD (1–3), TIMP2 and TIMP3 genes level were determined by real-time PCR analysis.

Results

We have seen the positive effects of SAHA on the TFK-1 cell line as it reduces cell viability and arresting cells in the G0/G1 phase. We also observed the negative effects of SAHA, as it increases the expression levels of YAP, TAZ, TGF-β protein and TEAD (1–3) gene. We also found that SAHA reduced the expression levels of TIMP2 and TIMP3 in TFK-1 cells, but was not statistically significant.

Conclusions

Although observing its antiproliferative effects, these negative effects may be related to the cells being resistant to the drug or the remaining cells having a more aggressive phenotype. Therefore, we think that caution should be exercised in the use of this drug for CCA treatment.

     

Immunohistochemical and ultrastructural changes in the renal cortex of cadmium-treated rats

The aim of this study was to determine the cadmium-induced immunohistochemical and morphological changes in the renal cortex of adult male rats exposed to high doses of cadmium for 30 d. Animals used as controls received a standard diet and water ad libitum. The animals used for this study received 15 ppm CdCl₂ in their drinking water for 1 mo. The mean arterial pressure (MAP), the mean blood Cd level, and the mean tissue Cd content were significantly higher when compared to controls (p < 0.01). Immunohistochemical studies demonstrated a weak labeling to type IV collagen and laminin, but a strong labeling to fibronectin in the renal cortex of the Cd-treated animals when compared to controls. The ultrastructural alterations found in Cd-treated rats were a diminution in the amount of filtration slits, increased fusion of foot processes in epithelial cells of the glomeruli, increase of lysosomal structures and pinocytic vesicles as well as large mitochondria in proximal tubule cells, and degenerated cells in distal tubules. Additionally, the glomerular basement membrane was slightly thickened. In conclusion, cadmium toxicity results in alterations in the renal extracellular matrix and tubular or glomerular cells, which could play an important role in renal dysfunction.