Israel Medical Association Journal

Objectives: To study the effects of purified allicin on the cardiovascular system.

Methods: Spontaneously hypertensive rats treated for 6 weeks with a daily dose of 80 mg/kg/day of purified allicin added to their chow were compared to control rats that were fed regular chow. Weight, systolic blood pressure (SBP), triglycerides, cholesterol, insulin and adiponectin were measured at baseline and at the end of the study.

Results: Allicin had no effect on body weight whereas it reduced SBP significantly from 190 ± 7.5 mmHg to 168 ± 5.7 (P < 0.0001) and triglyceride levels from 96 ± 25 mg/dl to 71 ± 19 (P =0.009). Allicin had no effect on plasma cholesterol, insulin and adiponectin levels.

Conclusions: Allicin lowers blood pressure and triglyceride levels in spontaneously hypertensive rats. This effect is not mediated through weight loss.

Background: In both adjuvant arthritis and rheumatoid arthritis edema and inflammation appear in synovial joints. Edema or effusion reflects an imbalance in lymph dynamics. Purified micronized flavonoid fraction is mainly used in the treatment of chronic venous insufficiency. This compound improves lymphatic drainage with a signicant increase in lymphatic flow and lymphatic pulsality. It is suggested that the beneficial effect of purified micronized flavonoid fraction may be involved in the treatment of adjuvant arthritis in rats.

Objectives: To evaluate the effect of Detralex on methotrexate prophylactic treatment of adjuvant arthritis in rats.

Methods: Groups of rats with adjuvant arthritis were treated with methotrexate (0.6 mg/kg/week), Detralex (20 mg/kg/day) and their combination for 50 days from adjuvant application. Hind paw swelling, arthrogram scores, serum albumin level, serum nitrite/nitrate concentrations, whole body mineral density and X-ray scans of synovial joints were evaluated as markers of inflammation and destructive changes associated with arthritis.

Results: Long-term prophylactic treatment with low dose methotrexate significantly inhibited the markers of both inflammation and arthritis. Detralex administered alone slightly decreased both the hind paw swelling and the arthritic score. Other inflammatory and arthritic markers were not significantly influenced. However, detralex combined with methotrexate markedly potentiated the beneficial effects of methotrexate, which resulted in a more significant reduction in hind paw swelling, arthritic scores, and serum concentrations of nitrite/nitrate. Interestingly, the arthritis-induced decrease of BMD[1] in AA[2] rats was significantly lower only in the group treated with the combination of Detralex+methotrexate.

Conclusion: Detralex increased the therapeutic efficacy of methotrexate basal treatment in AA. We suggest that this may be related to the beneficial effect of Detralex on microcirculation, especially on venules and lymphatic vessels.

Background: Halofuginone is a novel antifibrotic agent that can reserve the fibrotic process by specific inhibition of collagen type I synthesis.

Objectives: To evaluate the effect of Halo on the development of glomerulosclerosis and interstitial fibrosis in the 5/ 6 nephrectomy rat model.

Methods: Male Wistar rats were assigned to undergo 5/6 NX or sham operation, and then divided into three groups: 5/6 NX rats (NX-Halo and NX-Control) and sham. Systolic blood pressure proteinuria and body weight were determined every 2 weeks. At sacrifice (10 weeks) creatinine clearance was evaluated and remnant kidneys removed for histologic examination, Sirius red staining and in situ hybridization.

Results: Systolic blood pressure increased progressively in both 5/6 NX groups. Halo slowed the increase in proteinuria in 5/6 NX rats. As expected, creatinine clearance was lower in 5/6 NX groups when compared to sham rats. Creatinine clearance was significantly higher in the NX-Halo group at the end of the study period. Histologic examination by light microscopy showed significantly less severe interstitial fibrosis and glomerulosclerosis in Halo-treated rats. The increase in collagen α1 (I) gene expression and collagen staining after nephrectomy was almost completely abolished by Halo.

Conclusions: Halofuginone reduced proteinuria as well as the severity of interstitial fibrosis and glomerulosclerosis in 5/6 NX rats. The renal beneficial effect of Halo was also demonstrated by the blunted decrease in creatinine clearance observed in the treated animals.  
 

Background: Previous studies have demonstrated myocardial salvage by basic fibroblast growth factor administration following chronic myocardial ischemia or acute myocardial infarction.

Objectives: To study the effect of bFGF[1] on left ventricular morphometry following coronary occlusion and reperfusion episode in rats.

Methods: bFGF (0.5 mg) or placebo was continuously administered for a period of one week using an implanted osmotic pump. Animals were sacrificed 6 weeks after surgery and myocardial cross-sections were stained with Masson-trichrome and with anti-proliferating cell nuclear antigen antibody.

Results: LV[2] area, LV cavity diameter, LV cavity/wall thickness ratio, and injury size were unchanged compared with control animals. Proliferating endothelial cells were significantly more abundant in injured compared with normal myocardium, but with no differences between animals treated or not treated with bFGF.

Conclusions: One week of systemic bFGF administration following coronary occlusion and reperfusion had no additional effect on LV geometry or cellular proliferation in rats.

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[1] bFGF = basic fibroblast growth factor

[2] LV = left ventricular

Background: The method of midline Iaparotomy incision and closure remains a complex surgical problem.

Objective: To compare the mechanical properties at the interface of midline laparotomy incision made by scalpel versus electrocutting current in rats.

Methods: A sharp midline laparotomy incision was made in 60 Wistar female rats using a scalpel or electrocautery to open the fascia. The fascial and skin wounds were closed separately with a continuous nylon. Fascial specimens were analyzed for mechanical properties at the midline incision using a loading machine. The load-extension curve was recorded during tensile loading at a steady extension rate of 15 mm/mm.

Results: There was no statistically significant difference between the two groups in either wound-bursting force (PPEAK) or the strain energy spent until the point of measured PPEAK. Each load-extension curve showed a characteristic pattern in all rats. Tissue stiffness was greater in the scalpel group than in the electrocautery group (P= 0.02). Correlations were found between tissue stiffness and strain energy, between tissue stiffness and bursting force, and between bursting force and strain energy.

Conclusions: While tissue stiffness was greater when a scalpel was used compared to electrocutting to incise the midline abdominal fascia in rats, there was no difference in the bursing force required to disrupt the wound.

Objective: To study whether retinolpalmitate, beta-car­otene or lycopene could prevent liver cirrhosis induced by thioacetamide in rats.

Methods: In the control group liver cirrhosis was induced in male Wistar rats by intraperitoneal injections of TAA 200 mg/ kg for 12 weeks. The three study groups received in addition to TM either beta-carotene, lycopene or retinolpalmitate by gavage through an orogastric tube. Histopathological analysis and determination of the hydroxyproline contents of the livers were performed at the end of the protocol.

Results: Rats treated with beta-carotene and TAA had lower histopathologic scores and reduced levels of hepatic hydroxyproline (P= 0.02) than those treated by TAA alone. A trend of decreased fibrosis was observed in the rats treated with lycopene and TAA although this lacked statistical significance.

Conclusions: Beta-carotene attenuated liver cirrhosis induced by TAA in rats. The mechanism may be related to effects on hepatic stellate cells or to scavenging of free radicals by beta-carotene. Retinolpalmitate and lycopen had no significant beneficial effect.

Background: Exposure of newborn animals to high concentrations of oxygen leads to diffuse alveolar damage similar to that seen in bronchopulmonary dysplasia in human infants. Therefore, neonatal rats are a suitable practical model of hyperoxic lung damage in human infants.

Objective: To determine the involvement of tumor necrosis factor-alpha and interleukin-6 in lung injury in neonatal rats exposed to 100% O2 concentration.

Methods: A randomized controlled study was designed in which litters of term Sprague-Dawley rat pups were assigned to experimental or control groups. The pups in the experimental group were placed in 100% O2 from birth for 9 days, while the control pups were placed in room air. Twelve to 15 pups from each group were sacrificed on day 1, 3, 6, 9 and 13 after birth for bronchoalveolar lavage collection and lung histologic study. The bronchoalveolar lavage fluid was assayed for TNFα and IL-6.

Results: Newborn rats exposed to 100% O2 for the first 9 days of life showed severe pulmonary edema and hypercellularity on days 1 and 3, which then improved to nearly complete resolution on days 6 and 9. Pulmonary TNFα was produced early on O2 exposure (day 3) and pulmonary IL-6 later (days 6 and 9).

Conclusions: Hyperoxia induces sequential production of pulmonary TNFα and IL-6, which corresponds to the severity of the pathological findings and the known inflammatory and anti-inflammatory role of these cytokines.

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TNFα= tumor necrosis factor-alpha

IL-6= interleukin-6

Background: Cholestasis is a frequent problem in patients on total parenteral nutrition. Cisapride has a prokinetic effect on the biliary system, but its effect on hepatic excretory function is unknown.

Objectives: To study the effect of cisapride on TPN-induced cholestasis in a rat model.

Methods: Bile flow and bile salt secretion rate were measured in rats given TPN. There were four groups of 8 to 13 animals each. After a one hour baseline period during which all four groups received i.v. saline infusion, two groups received a TPN solution for another 2 hours, while saline was infused in the two control groups.

At the beginning of the second hour, 2 mg/kg cisapride was injected i.v. as a bolus into one experimental and one control group. Bile was collected from the common bile duct.

Results: At the end of the third hour, TPN caused a significant reduction in bile flow (P<0.02) and bile salt secretion rate (P<0.001) (61.24 vs. 50.74 µl/min/kg, and 1.173 vs. 0.799 µmol/min/kg, respectively). Addition of cisapride abolished the cholestatic effect of TPN.

Conclusions: Cisapride has a protective effect against TPN-associated cholestasis. This may have clinical significance, and further studies are warranted.

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TPN= total parenteral nutrition