Neuroprotective effects of pramipexole against tunicamycin‐induced cell death in PC12 cells

• 1 Pramipexole (PPX), a dopamine D2 and D3 receptor agonist, exerts neuroprotective effects via both dopamine receptor‐mediated and non‐dopaminergic mechanisms. In the present study, we demonstrate that PPX reduces the toxicity of tunicamycin, a typical endoplasmic reticulum (ER) stressor, in PC12h cells, a subline of PC12 cells.
• 2 The PC12h cells were treated with 300 μmol / L PPX in the presence of 0.5 μmol / L tunicamycin for 24 h. The neuroprotective effects of PPX against tunicamycin‐induced cell death were evaluated using 3‐(4,5‐dimethyl‐2 thiazoyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release assays, Hoechst 33258 staining and western blot analysis.
• 3 Tunicamycin (0.2, 0.3 and 0.5 μg / mL) dose‐dependently decreased MTT activity and increased LDH release from PC12h cells. Treatment with 300 μmol / L PPX rescued the tunicamycin‐induced decrease in cell viability.
• 4 Spiperone (10 μmol / L), a dopamine D2 and D4 receptor antagonist, had no effect on PPX neuroprotection against tunicamycin in these cells. Marker proteins of ER stress and apoptosis are known to be upregulated by tunicamycin, but we detected no significant effects of PPX on these factors.
• 5 In conclusion, we speculate that a combination of several mechanisms may be involved in PPX‐induced neuroprotection.

     

Bioavailability of Soil-Bound TCDD: Dermal Bioavailability in the Rat

Bioavailability of Soil-Bound TCDD: Dermal Bioavailability inthe Rat. SHU, H., TEITELBAUM, T., WEBB, A. S., MARPLE, L., BRUNCK,B. DEI ROSSI, D., MURRAY, J., AND PAUSTENBACH, D. (1988). Fundam.Appl. Toxicol. 10, 335-343. 2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD), an unwanted by-product formed during the manufactureof hexachlorophene and phenoxyherbicides, has been found asan environmental contaminant in many U.S. and Western Europeansites. This study examines in the rat the degree of dermal absorptionof TCDD bound to soil. Such information would assist regulatoryagencies in evaluating the degree of exposure of humans whocome in contact with TCDD-contaminated soil. Several parameterswhich may influence dermal absorption were studied, includingTCDD dose, duration of contact, presence of crankcase oil asa co-contaminant, and environmentally contaminated vs laboratory-preparedsoil. The dermal penetration of TCDD following 4 hr of contactwith skin was approximately 60% of that following 24 hr of contact(P 0.05). Following 24 hr of contact with the skin, the degreeof dermal uptake of TCDD contaminated soil was approximately1% of the administered dose. Under the conditions of the presentstudy, the degree of uptake does not appear to be influencedto any significant extent by the concentration of TCDD on soil,the presence of crankcase oil as co-contaminants, or by environmentallyvs laboratory-contaminated soil. Although a number of parametersexamined in this study did not significantly influence the degreeof dermal absorption of TCDD in the rat following 24 hr of contactwith the contaminated soil, the unqualified use of the 1% valueto estimate human exposure would overestimate human exposure,since there is general agreement among researchers that ratskin tends to be more permeable than human skin to highly lipid-solublecompounds such as TCDD.     

Effects of Cardiomyoplasty on Cardiac Growth in Rats

A bstract Background and aim of the study : Cardiomyoplasty (CMP) has been proposed as a treatment for pediatric patients, but restriction of cardiac growth by the muscle wrap is a potential source of concern. This possibility was investigated in an immature animal model. Methods : Six-week-old rats (body weight 203.8 ± 5.4 g, mean ± SEM) underwent either left thoracotomy with CMP (group I, n = 7), or thoracotomy without CMP (group II, n = 8). A third group (group III, n = 7) served as untreated controls. Final measurements were made 20 weeks later after body weights had reached a plateau. Results : Preoperative body weights were not significantly different between the groups. At elective sacrifice, the body weights of animals that underwent surgery did not differ significantly (group I, 558.0 ± 21.5 g and group II, 617.3 ± 20.3 g), but were significantly less than those of control animals (727.6 ± 13.3 g, p < 0.001 and p < 0.01, respectively). Cardiac ventricular weights in the CMP group were significantly less than those of control animals (group I, 1.21 ± 0.06 g; group III 1.45 ± 0.04 g; p < 0.01), but were not statistically different from those of the sham thoracotomy group (group II, 1.36 ± 0.05 g). Mean left ventricular end-diastolic volumes were similar in all groups (group I, 0.67 ± 0.07 mL; group II, 0.66 ± 0.07 mL; and group III, 0.69 ± 0.10 mL; p = ns). Conclusions : A major surgical procedure impairs growth in juvenile rats. No evidence emerged from this study for additional restriction of cardiac development due to cardiac wrapping. However, studies that include stimulated muscle wraps are needed before CMP should be considered for the pediatric age group.     

Graphical analysis of data from pharmacology experiments

Dose-response curves are often used in the study of the interaction of hormones and receptors. From these plots, IC50 or EC50 values are calculated. In these pharmacological assays it is implicitly assumed that a single receptor predominates in a tissue. In this paper the interaction of a ligand with two receptors is studied from a theoretical point of view. It is assumed that the responses mediated by these receptors are qualitatively or quantitatively different. The theoretical direct and Scatchard plots display a high variety of shapes depending upon the difference in potency of the effect of the drug acting in both receptors and upon the magnitude and sign of the individual response. When dose-response curves taken from the literature have been transformed into direct or Scatchard plots new information has become available. With respect to this, it is shown that agonists of purinergic receptors seem to interact with two different populations of receptors. We claim that carefully designed experiments must provide valuable information concerning the number of subtypes of receptors present in a given system and the kind of response mediated by them.     

Immunological identification of A1 adenosine receptors in brain cortex

The A₁ adenosine receptor from pig brain cortex has been identified by means of two antipeptide antibodies against two domains of the receptor molecule: PC/10 antiserum was raised against a part of the third intracellular loop, and PC/20 antiserum was raised against a part of the second extracellular loop. PC/10 antibody was able to recognize a 39-kDa band that corresponded to the A_l receptor, as demonstrated by immunoblotting and by immunoprecipitation of the molecule cross-linked to [¹²⁵I](R)-2-azidoN²-p-hydroxy(phenylisopropyl)adenosine. Besides the 39-kDa band, PC/20 also recognized a 74-kDa form that does not seem to correspond to a receptor-G protein complex. The occurrence of the two bands was detected and analyzed in samples from different species and tissues showing a heterogeneous distribution of both. The 74-kDa form can be converted into the 39-kDa form by treatment with agonists or antagonists of A_l adenosine receptors. These results suggest that A₁ adenosine receptor can occur in dimers and that the dimer–monomer conversion might be regulated by adenosine as the physiological ligand. Since the 74-kDa aggregates were not recognized by PC/10, it is likely that part of the third intracellular loop participates in the protein–protein interaction. ©1995 Wiley-Liss, Inc.     

Immunological effect of aqueous extract of Vernonia amygdalina and a known immune booster called immunace® and their admixtures on HIV/AIDS clients: a comparative study

Objective

To investigate the immunological effect of Vernonia amygdalina (V. amygdalina) leaf extract and immunace^® on HIV infected patients taking highly active antiretroviral therapy.

Methods

Fresh V. amygdalina leaves were collected within Nsukka area in Enugu State. The leaves were rinsed with distilled water. Two handful of cleaned fresh leaves were soaked in 200 mL water and squeezed gently by hand to a mixture. Clients were divided into four groups and each group was given different combination. They took the medication for four weeks. The immune effect was tested against marketed immune booster in some retroviral clients.

Results

The mean absolute CD4 count was increased in the client who took the extract or supplement. And the clients who took both the extract and supplement had a greater increase in the CD4 count. The increased CD4 was significant as compared with the control group (P<0.05). The skin rashes were also improved in the entire groups.

Conclusions

It can be concluded that the aqueous extract of V. amygdalina and immunace or both have immunological effect on HIV infected patients. Therefore, we suggest that the V. amygdalina extract or immunace or both could be used as adjuvant in the management of HIV/AIDS clients.     

The two-state dimer receptor model: a general model for receptor dimers

Nonlinear Scatchard plots are often found for agonist binding to G-protein-coupled receptors. Because there is clear evidence of receptor dimerization, these nonlinear Scatchard plots can reflect cooperativity on agonist binding to the two binding sites in the dimer. According to this, the "two-state dimer receptor model" has been recently derived. In this article, the performance of the model has been analyzed in fitting data of agonist binding to A(1) adenosine receptors, which are an example of receptor displaying concave downward Scatchard plots. Analysis of agonist/antagonist competition data for dopamine D(1) receptors using the two-state dimer receptor model has also been performed. Although fitting to the two-state dimer receptor model was similar to the fitting to the "two-independent-site receptor model", the former is simpler, and a discrimination test selects the two-state dimer receptor model as the best. This model was also very robust in fitting data of estrogen binding to the estrogen receptor, for which Scatchard plots are concave upward. On the one hand, the model would predict the already demonstrated existence of estrogen receptor dimers. On the other hand, the model would predict that concave upward Scatchard plots reflect positive cooperativity, which can be neither predicted nor explained by assuming the existence of two different affinity states. In summary, the two-state dimer receptor model is good for fitting data of binding to dimeric receptors displaying either linear, concave upward, or concave downward Scatchard plots.     

Seroepidemiology of measles in Catalonia (Spain) 1985–1986

A seroepidemiological study of measles immunological status was carried out among four different populations: schoolchildren of 6–7 years, 10–11 years and 13–14 years, and pregnant women of 18–45 years, in Catalonia, Spain; 1,213 children and 239 pregnant women were surveyed. The measurement of measles antibodies was made by indirect immunofluorescence, with antibody titres 1:8 considered as positive.The prevalence of measles antibodies was 82.9% in the 6–7 year old group, 87.2%, in the 10–11 year old group and 94.4% in the age group 13–14 years. Among pregnant women, the prevalence of antibodies was 96.2%.Two of the variables studied were associated with the prevalence of measles antibodies in schoolchildren: the disease antecedents and measles vaccination. In pregnant women aged 18–45 no variable had any stastically significant association with the prevalence of measles antibodies.     

1，25-二羟维生素D3对糖尿病大鼠肺脏的保护作用及机制

目的观察1,25-二羟维生素D3[1,25-（OH）：D,]对糖尿病大鼠炎性水平及肺组织Toll样受体4（TLR4）表达的影响,探讨其肺保护作用及机制。方法将90只SD大鼠随机分为对照组（C组）10只及模型组80只,模型组经尾静脉注射STZ制备糖尿病模型,C组注射等体积柠檬酸缓冲液;将模型组造模成功的75只大鼠随机分为糖尿病组（D组）,1,25-（OH）：D,大、中、小剂量干预组（H、M、L组）及精蛋白锌胰岛素干预组（Y组）各15只,其中H、M、L组分别予0．3、0．15、0．025μg/（kg·d）的1,25-（OH）：D3灌胃,Y组予胰岛素颈后皮下注射,c组和D组予蒸馏水2mL灌胃,均为1次/d、连续16周,16周后所有动物均采用股动脉放血处死,立即取肺脏组织置于10％甲醛及液氮中保存。测定各组血糖及血清CRP水平;采用HE、Masson染色法观察肺组织形态学变化,免疫组织化学法检测TLR4、NF-KBp65的蛋白表达;采用PCR法定量检测TLR4、MyD88、NF-KBp65的mRNA表达。结果①D组血糖及血清CRP水平均显著高于C组（P〈0．01）,各干预组均不同程度低于D组,尤以H组为著（P〈0．01）。②D组肺泡壁重度增厚、肺间质明显增生、大量炎症细胞浸润,H、Y、M及L组肺泡壁轻到中度增厚、炎细胞浸润明显;与c组比较,余5组TLR4、NF-KBp65蛋白表达有所升高,其中H、Y组显著低于D组。③D组,TLR4、MyD88和NF-KBp65的mRNA表达显著高于C组（P〈0．01）,各干预组表达水均低于D组。肺组织TLR4mRNA表达与MyD88mRNA（r=0．610）、NF-KBp65mRNA表达（r=0．744）均呈正相关,P均〈0．001;MyD88mRNA与NF-KBp65mRNA表达亦呈正相关（r=0．609）,P〈0．001。结论1,25-（OH）：D,可能通过TLR4介导的炎症途径对STZ诱导的糖尿病大鼠肺脏病变发挥保护作用。     

Acute pancreatitis caused by salazopyrine. An unusual association]

A 28 year old patient with a moderate attack of ulcerative colitis was treated with sulfasalazine. Ten days after, the patient was admitted with clinical and laboratory symptoms of acute pancreatitis (serum amylase 631 u., serum lipase 1080 u. urine amylase, 910 u.). Upon recovery, sulfasalazine was reintroduced at lower dosage (2 Gm/day), and the patient repeated the clinical and biological picture of acute pancreatitis (serum amylase of 710 and lipase 1010 u.) CAT scan showed pancreatic edema and ultrasonography demonstrated a normal gallbladder. The symptoms and laboratory abnormalities disappeared in three days after stopping sulfasalazine. The patient has been followed-up for one year without recurrence of pancreatitis on maintenance treatment with 1.5 Gm 5-Aminosalicylic acid.