سال:1380 | دوره: | شماره: |تعداد مقالات:10

The glomerular mesangial cells (GMC) play a central role in the synthesis and turnover of the glomerular mesangial matrix. The breakdown of the matrix likely depends on the balance between of a variety of proteinases including matrix metalloproteinases and their biological inhibitors secreted by the GMC, and any disturbance in the balance may result in appearance of various pathological states such as glomerulosclerosis. We therefore studied pattern secretion of matrix metalloproteinases (MMPs), MMP-1, MMP-2, MMP-3, MMP-9 and their biological tissue inhibitor of matrix metalloproteinases (TIMPs), TIMP-1 and TIMP-2 by cultured human GMC. We also measured MMP-1/TIMP-1 complex level in the cell culture supernatants. For this purpose, the GMC were incubated under serum-free conditions with medium (RPMI-1640) alone or in combination with TNF- a (30 ng/ml) or phorbol myristate acetate (PMA) (50 ng/ml) for exactly 24, 48 and 72 hours. The above parameters were assayed by established ELISA techniques. Our results showed that the lowest and largest secretions were related to MMP-9 and MMP-2, respectively. The results indicated that the MMPs and TIMPs secretion were increased by TNF-a (MMP-1, MMP-2, TIMP-1 and TIMP-2) and PMA (MMP-2, TIMP-1 and TIMP-2), significantly (P<0.05). These results suggest that the GMC can synthesis and release various MMPs and their inhibitors (TIMPs) that, in part, control turnover of extracellular matrix proteins.

Human nonspecific polyclonal IgG and granulocytes, which accumulate in inflammation foci, were radiolabeled with 125I and ¹¹¹In-Tropolone, respectively. Biodistribution of these two radiolabels was assessed in normal and inflammation-induced mice. 125I-IgG showed better localization to the inflammated areas. Blood levels with ¹¹¹In-Tropolone leukocytes were lower at all time points. In addition, the inflammatory thigh-to-blood ratios showed an improvement, whereas the ratios of inflammatory thigh-to-other normal tissues were higher for 125I-IgG than ¹¹¹In-Tropolone leukocytes. In conclusion, labeled IgG due to better localization in inflammated sites and higher target-to-background ratios is more suitable agent than labeled leukocytes for immunoscintigraphy of inflammation.

Dextransucrase of Leuconostoc mesenteroides PTCC 1059 is an enzyme of industrial and medical interest that catalyzes the synthesis of a soluble dextran from sucrose. The mutant strains of Leuconostoc mesenteroides PTCC 1059 hyperproducing for dextransucrase were isolated after UV irradiation and treatment with ethyl methane sulfonate. The enzyme activity of one mutant strain, the 1059M5E4, was about 2.5-fold higher than that of the wild type, while its cell growth was relatively lower. The 1059M5E4 dextransucrase produced the same type of dextran as well as the wild type but showed higher thermal stability. These properties may be interesting for using this strain in enzymatic production of dextran.

The effect of prenatal chronic lead exposure on pentylenetetrazol (PTZ)-induced kindling parameters (seizure index, seizure latency and seizure stage) in rats was studied. Adult female rats with a weight range of 140-180 g were selected and pretreated with lead acetate (0.05% w/v) orally, 25 days prior to mating. The control group was given distilled water containing sodium acetate solution (0.05% w/v). After delivery, treatment was ceased, and after lactation, male neonates were separated from the females in both groups. After maturation of male rats, the PTZ-kindling was induced by daily interapritoneally injection of PTZ (30 mg/kg). Kindling parameters in the control and treated groups were determined. The results indicated that animals with prenatal lead exposure have full kindling state with 9-19 (16.87±1.54) injections, whereas this value for control group was 12-23 (18.62±1.48) injections. The seizure latency for the treated group was lower (P<0.05) than the control (2.29±0.44 min versus 3.65±0.45 min). The seizure severity (regarding to seizure index) was statistically higher in the treated group (P<0.05). The seizure stages were also different in the treated and control groups (P<0.05). The seizure frequency of first and second stages of kindling in the control group was higher than that of treated one (P<0.05). Also the seizure frequency in the third and fourth kindling stages of case group was higher than controls (P<0.05). It is concluded that prenatal lead exposure alters seizure susceptibility in rat PTZ-Kindling model.

The hydrodistilled aerial parts oil of Pycnocycla spinosa var. spinosa was analyzed by GC and GC/MS. Thirty three components were identified. Geranyl isovalerate (14.9%), caryophyllene oxide (10.6%), a-eudesmol (9.2%) b-citronellol (7.2%), elemicin (6.8%), r-cymene (4.7%), citronellyl acetate (4.3%), and a-cadinol (3.3%) were found as major components.

Addition of Cr VI (dichromate) to isolated rat hepatocytes results in rapid glutathione oxidation, reactive oxygen species (ROS) formation, lipid peroxidation, decreased mitochondrial membrane potential and lysosomal membrane rupture before hepatocyte lysis occurred. Cytotoxicity was prevented by ROS scavengers, antioxidants, and glutamine (ATP generator). Hepatocyte dichlorofluorescin oxidation to dichlorofluorescein (DCF) to determine ROS formation was inhibited by mannitol (a hydroxyl radical scavenger) or butylated hydroxyanisole and butylated hydroxytoluene (antioxidants). The Cr VI reductive mechanism required for toxicity is not known. Cytochrome P450 inhibitors, Particularly CYP 2E1 inhibitors, but not inhibitors of DT diaphorase or glutathione reductase also prevented cytotoxicity. This suggests that P450 reductase and/or reduced cytochrome P450 contributes to Cr VI reduction to Cr IV. Glutathione depleted hepatocytes were resistant to Cr (VI) toxicity and much less dichlorofluorescin oxidation occurred. Reduction of dichromate by glutathione or cysteine in vitro was also accompanied by oxygen uptake and was inhibited by Mn II (a Cr IV reductant). Cr VI induced cytotoxicity and ROS formation was also inhibited by Mn II, which suggests that, Cr IV and Cr IV GSH mediate "ROS" formation in isolated hepatocytes. In conclusion Cr VI cytotoxicity is associated with mitochondrial/lysosomal toxicity by the metabolic reactive intermediate Cr IV and “ROS”.

Glycyrrhetinic acid is a major component of a traditional plant called Licorice. This substance has been found to have some pharmacological properties including anti-inflammatory, anti-viral, anti-bacterial, anti-fungal, anti-allergic, anti-carcinogenic and anti-peptic-ulcer. Glycyrrhetinic acid also affects against some parasites such as Trichomonas vaginalis. In this study, 55 hospital strains of Staphylococcus aureus and 32 Actinobacillus actinomycetemcomitans, were isolated from patient’s specimens by culture method. Antibacterial activities of glycyrrhetinic acid against those microorganisms were investigated by determining minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) methods. The MIC for S. aureus and A. actinomycetemcomitans were 64 and 8 mg/ml respectively. The MBC for S. aureus and A. actinomycetemcomitans were 64 and 16 mg/ml respectively. It is concluded that Glycyrrhetinic acid is effective against Staphylococcus aureus and Actinobacillus actinomycetemcomitans in appropriate concentrations.

The discovery that 1,4-dihydropyridine (DHP) class of calcium channel antagonist inhibits the Ca+2 influx represented a major therapeutic advance in the treatment of cardiovascular diseases such as hypertension, angina pectoris and other spastic smooth muscle disorders. A novel class of calcium channel antagonist of flunarizine containing arylpiperazinyl moiety has recently been reported. It was therefore of interest to determine the effect that selected C-3 substituents contained amino alkyl and arylpiperazine, in conjunction with a C-4 1-methyl-5-nitro-2-imidazolyl substituents on calcium channel antagonist activity. The unsymmetrical analogues were prepared by a procedure reported by Meyer in which 1-methyl-5-nitro-imidazol-2-carboxaldehyde was reacted with acetoacetic esters and alkyl 3-aminocrotonate. In vitro calcium channel antagonist activities were determined by the use of high K+ contraction of guinea pig ileal longitudinal smooth muscle. All compounds exhibited comparable calcium channel antagonist activity (IC-950=10 to 10 -11M) against reference drug nifedipine (IC50= 2.75±0.36x 10-10 M).

Three versions of a new dry powder inhaler (DPI), RG-haler, were designed using two kinds of grid inserts. Salbutamol sulfate/lactose blend (Ventolin Rotacaps®) was selected as a model formulation to analyze the performance of all inhalers and compare their efficiency with three marketed devices (Rotahaler®, Spinhaler® and ISF inhalator®) using the twin impinger (TI). Deposition of the drug in device was significantly (P<0.05) lower for ISF inhalator® and all kinds of RG-halers in comparison with those of Rotahaler® and Spinhaler®. The amount of drug deposited in the stage 2 and the respirable dose for RG-halers were similar to those of ISF inhalator® and significantly (P<0.05) higher than those of Rotahaler® and Spinhaler®. The results suggest efficient aerosol generating capability of the RG-haler.

In the present study the effects of lead acetate and/or L-Arginine as a nitric oxide precursor and L-NAME as a nitric oxide synthase inhibitor on the amylase secretion of rat parotid gland lobules were investigated. Lead acetate in doses of 3, 30 and 300  mM significantly (P<0.01) caused a dose-dependent reduction in isoproterenol-stimulated or non-stimulated amylase secretion. When secretion of saliva was not stimulated by beta-adrenergic agonist, L-Arginine (100 mM) significantly (P<0.01) reduced amylase output. L-NAME (100 mM) alone had no significant effect on amylase output but when used with lead acetate prevented (P<0.01) from lead-induced reduction of amylase output. Both L-NAME (100 mM) and L-Arginine (100 mM)) when used alone reduced isoproterenol-stimulated amylase output. Concurrent administration of lead acetate (300 mM)) with either L-Arginine (100 mM) or L-NAME (100 mM) showed a marked positive interaction in reducing the isoproterenol-stimulated secretion of amylase. These findings suggest that nitric oxide plays a role in secretion of amylase from parotid. Different affinity of lead acetate to interact with different nitric oxide synthases might be a reason for different effects on parotid amylase secretion observed in the presence or absence of secretion stimulant.