Garlic (Allium sativum L.) as a potential antidote for cadmium and lead intoxication: cadmium and lead distribution and analysis in different mice organs.

Analysis and distribution of Pb and Cd in different mice organs including liver, kidney, spleen, heart and blood were evaluated after treatment with different aqueous concentrations of garlic (12.5-100 mg/l). Atomic absorption spectrometry (AAS) was used for analysis of Pb and Cd in these organs. Treatment of Cd-Pb exposed mice with garlic (12.5-100 mg/l) reduced Pb concentrations by 44.65, 42.61, 38.4, 47.56, and 66.62% in liver, kidney, heart, spleen and blood respectively. Moreover, garlic reduced Cd levels by 72.5, 87.7, 92.6, 95.6, and 71.7% in liver, kidney, heart, spleen and blood respectively. The suppressed immune responses in mice pretreated with Cd-Pb mixture were reversed by 48.85, 55.82, 81.4 and 90.7 in the presence of 100, 50, 25, and 12.5 mg/ml of garlic extract.

The use of medicinal herbs by diabetic Jordanian patients.

Diabetes mellitus is the most common metabolic disorder worldwide. To date, there have been no reports on the frequency of use of herb medicines in the managements of diabetes mellitus in Jordan. This cross-sectional study was conducted by interviewing 310 diabetic patients visiting two medical centers in Jordan: Jordan University of Science & Technology Medical Center and Sarih Medical Center between December 2003 and August 2004. It is found that 31% of interviewed patients have used herbal products (96 patients). The results revealed that the most commonly used herbs by diabetic patients in Jordan were Trigonella foenumgraecum (22.9%), Lupinus albus (14.6%), Allium sativum (11.5%), Allium cepa (5.2%), Nigella sativa (7.3%), Zea mays L. (6.3%), Urtica dioica L. (8.3%), Eucalyptus globules LA (9.4%), Olea europea L. (3.1%), Cumminum cyminum (9.4%), Coriandrum sativum (10.4%), Salvia officinalis L. (3.1%), and Tilia cordata (1%). Furthermore, it is found that 47.9% of the patients used herbs according to advice from their friends on a daily basis. The side effects were reported by 36.5% of the patients and include headache, nausea, dizziness, itching, palpitation, and sweating. Among the patients, 72.9% used the herbs as adjunctive therapy along with their anti-diabetic drugs and 80.2% of the patients informed their physicians about their use. A 79.2% of the sample confirmed their intention to re-use these herbs as 86.5% of them were satisfied with their diabetes control. There was a significant relationship between the use of herbs, the patient's place of residence and his/her level of education. The main conclusion of this survey is that the use of medicinal herbs among diabetic patient in Jordan is common. Therefore, it is essential to increase the level of awareness among diabetic patients and health care providers regarding the efficacy and toxicity of these medicinal herbs.

Azathioprine transport through rat skin and its immunosuppressive effect.

The objective of this research was to study the in vitro and in vivo percutaneous absorption of azathioprine with and without the effect of penetration enhancers. In vitro permeation of azathioprine was studied using a Franz diffusion cell and rat skin. Both azathioprine and 6-mercaptopurine were detected in the receiver solution with a reversed phase HPLC system. The steady state flux of azathioprine, permeability coefficient, and lag time were reported. Penetration enhancers such as dimethylsulfoxide (DMSO), dimethylformamide (DMF), and urea were added to the donor compartment to increase the skin permeation of azathioprine. The flux of azathioprine was increased by 20.7%, and 22.4% using dimethylsulfoxide, and dimethylformamide respectively. The in vivo permeation was determined by measurement of antibody titers by the slide latex agglutination test. The in vivo permeation study showed that the titers of antibody induced in the rats were not affected by topical application of azathioprine solution. The results show that azathioprine has low flux to exert a systemic effect with and without penetration enhancers. However these results may support the use of topical azathioprine for the treatment of some dermatological disorders with minimum side effects.

Adenine phosphoribosyltransferase deficiency: a simple diagnostic test.

1. A simple method for diagnosing adenine phosphoribosyltransferase (APRT) deficiency using urine is described. 2. T.l.c. of 1 microliter urine from a child with APRT deficiency was performed and adenine was easily detected by its brilliant blue phosphorescence at liquid nitrogen temperature. 3. Four physicochemical characteristics of adenine were recorded: RF value, and the colour, decay time and pH sensitivity of phosphorescence. 4. Adenine was not detected in the urine of 116 subjects used as controls. These included healthy individuals and patients with inherited metabolic disorders, diseases of purine metabolism and of the kidney and urinary tract. Some of them were taking a variety of drugs including purine derivatives. 5. The test correctly diagnosed three cases of APRT deficiency out of 10 urine samples tested blind.

Does 2-mercaptoethane sulphonate (mesna) prevent cyclophosphamide and azathioprine induced immunosuppression? In vitro studies.

The effect of 2-mercaptoethane sulphonate (mesna) on the inhibition of the human MLR by 4-hydroxycyclophosphamide or azathioprine was studied. 4-Hydroxycyclophosphamide (34 microM) completely inhibited the MLR and this inhibition was unaffected by 122 microM of 2-mercaptoethane sulphonate or its disulphide. At high concentrations (mM) 2-mercaptoethane sulphonate inhibited the MLR reaching 85% at 24 mM. 2-Mercaptoethane sulphonate (15-122 microM) had no effect on azathioprine (36 microM) inhibition. The results of these in vitro studies suggest that 2-mercaptoethane sulphonate does not interfere with cyclophosphamide or azathioprine induced suppression of cellular immunity.

Azathioprine suppresses the mixed lymphocyte reaction of patients with Lesch-Nyhan syndrome.

The mixed lymphocyte reaction of Lesch-Nyhan patients (HGPRT deficient) was used to study the immunosuppressive effects of azathioprine and 6-mercaptopurine (6-MP). Mitogen stimulated lymphocytes of these patients are highly resistant to azathioprine and 6-MP. When both stimulator and responder lymphocytes in the MLR were HGPRT deficient, azathioprine (36 microM) was much more inhibitory than 6-MP (100 microM). Azathioprine produced inhibition of 98.2% and 78.5% compared with the values of 63.9% and 30.6% for 6-MP. The difference in inhibitory activity between azathioprine and 6-MP was reduced when normal stimulator lymphocytes were cultured with HGPRT deficient responder lymphocytes in the MLR. These results provide very strong evidence that the nucleotide metabolites of azathioprine and 6-MP are unnecessary for immunosuppression. They also suggest that azathioprine and 6-MP interfere with antigenic triggering of the MLR.

Strength of the human mixed lymphocyte reaction (MLR) and its suppression by azathioprine or 6-mercaptopurine.

Azathioprine (36 microM) had a significantly (P less than 0.00003) greater inhibitory effect on human MLR responses below 20,000 counts/min than on responses above 20,000 counts/min. In contrast, 6-mercaptopurine (100 microM) had a similar suppressive effect on MLR responses below and above 20,000 counts/min suggesting it has a different mode of action to azathioprine.

Lack of inhibition of purine nucleoside phosphorylase and adenosine deaminase in patients treated with azathioprine.

Deficiency of the purine salvage enzymes purine nucleoside phosphorylase (PNP) and adenosine deaminase (ADA) are known causes of immunodeficiency. Evidence for inhibition of these enzymes was sought in 16 patients on azathioprine therapy by testing for deoxyguanosine (PNP deficiency) and deoxyadenosine (ADA deficiency) in urine using a novel phosphorescence method. These abnormal nucleosides were not found in urine of azathioprine treated patients or in 30 normal controls but were easily detected in urine from proven cases of PNP and ADA deficiency suggesting lack of in vivo inhibition of PNP and ADA by azathioprine.

Immune deficiency due to adenosine deaminase and purine nucleoside phosphorylase deficiency: a simple diagnostic test.

A simple method is described for diagnosing adenosine deaminase and purine nucleoside phosphorylase deficiency using urine. Cellulose thin layer chromatography of 1 microliter of urine from affected children was performed and deoxyadenosine and deoxyguanosine were easily detected by phosphorescence at the temperature of liquid nitrogen. This test is not expensive and can be done in any laboratory. It should be suitable for diagnostic screening in patients with immune deficiency.

Effect of levamisole and azathioprine on the human mixed lymphocyte reaction (MLR).

Levamisole (1.25-4.15 microM) had no effect on tritiated thymidine incorporation into DNA of mixed lymphocyte cultures. Moreover, it did not cause any reversal of azathioprine (18-36 microM) inhibitory effects on the MLR.

Azathioprine and 6-mercaptopurine (6-MP) suppress the human mixed lymphocyte reaction (MLR) by different mechanisms.

6-MP inhibitory effects on the MLR were reversed by AIC (46%), adenine (32%), hypoxanthine (89%), adenosine (86%) and inosine (93%). AIC, adenine, hypoxanthine and inosine had no effect on azathioprine inhibition of the MLR. Adenosine at 10 microM caused 29% reversal and had no effect at 100-400 microM on azathioprine inhibition of the MLR. Reversal of 6-MP suppression of the MLR was decreased with the delay of adenosine addition. Guanine, xanthine and guanosine caused no reversal of 6-MP or azathioprine inhibitory effects on the MLR. These results show that azathioprine and 6-MP suppress the MLR by different mechanisms.