Investigation of the antispasmodic potential of Hibiscus sabdariffa calyces

Addition of an aqueous extract of Hibiscus sabdariffa calyces (2.5 ml/bath approximately 125 mg of starting crude material) inhibited the tone of various isolated muscle preparations (rabbit aortic strip, rhythmically contracting rat uterus, guinea-pig tracheal chain and rat diaphragm). Other muscles were stimulated (quiescent rat uterus and frog rectus abdominis). Intravenous injection of the extract to anaesthetized cats lowered the blood pressure in a dose-response manner. The inhibitory effects were resistant to a number of standard receptor blockers but the hypotensive influence was partially blocked by atropine and the tonic effects on rat uterus were partially reduced by hydrocortisone and indomethacin.     

Topical anaesthesia in haemodialysis: Evaluation of topical anaesthesia with lidocaine during vascular access in children undergoing long-term haemodialysis for chronic renal failure

Türkmen M, Kavukçu S, Soylu A, Ay N, Sevinç N, Sersan R. International Journal of Nursing Practice 1997; 3: 79–83
Topical anaesthesia in haemodialysis: Evaluation of topical anaesthesia with lidocaine during vascular access in children undergoing long-term haemodialysis for chronic renal failure
Children with chronic renal failure are frequently exposed to painful invasive procedures. Ointments containing lignocaine-prilocaine, when used before intravenous punctures, have been reported to lessen the pain sensation. The aim of this study was to interpret the effectiveness of lidocaine 2.5% ointment in preventing pain when used before venous and arterial punctures in children undergoing a haemodialysis programme for chronic renal failure. Eight children were included in this study. The pain level was identified by the patients using a linear analogue scale. When topical anaesthetic and placebo were compared, there was no statistical difference in interpretation of pain during arterial ( P >0.4), venous ( P >0.375) or both ( P >0.4) procedures. We conclude that lidocaine 2.5% ointment is not effective in preventing pain in children undergoing long-term haemodialysis. In these patients some other factors, like psychological factors, puncture technique and needle size must be taken into consideration for the prevention of pain.     

Maximal thymectomy in children with myasthenia gravis.

OBJECTIVES: We performed this study to evaluate the benefit of thymectomy in children with myasthenia gravis (MG). METHODS: Over a period of 15 years from 1986 to 2001, we collected data on 30 children with MG and retrospectively reviewed the outcome of maximal thymectomy. RESULTS: There were 23 females and seven males with a mean age of 13.2 years (range 4-16). The mean duration of the disease was 19.3 months (range 2-144). According to Osserman classification, there were 14 children in class II; 12 in class III; and four children in class IV. One child in class IV required postoperative ventilation and one was re-explored to drain a pericardial effusion secondary to central line leak. We found ectopic thymic tissue in 10 cases (33.3%). During a mean follow-up period of 53.5 months (range 9-180), complete remission was noted in 13 children (43.4%) and improvement in 14 (46.6%). The remaining three children (10%) did not improve following surgery. Univariate analysis (P < 0.05) showed that ectopic thymic tissue is a significant prognostic factor for outcome. CONCLUSION: Maximal thymectomy appears to provide a high rate of remission and improvement in children with MG. However, the presence of ectopic thymic tissue has poor prognostic value.     

Muscular dystrophy associated with β-dystroglycan deficiency

β-Dystroglycan, a 43-kd transmembrane dystrophinassociated glycoprotein, plays an important role in linking dystrophin to the laminin-binding α-dystroglycan. α-/β-Dystroglycan is encoded by a single gene on chromosome 3p21 and ubiquitously expressed in muscle and nonmuscle tissues. No known human diseases have been mapped to this locus. Here, we describe the selective deficiency of β-dystroglycan in a 4-year-old Saudi boy with muscular dystrophy. The patient had a borderline elevation of serum creatine kinase level and early-onset proximal symmetrical muscle weakness and wasting without calf hypertrophy. The milder phenotype may suggest a secondary deficiency of β-dystroglycan; however, the unique immunofluorescence labeling suggests that the patient may present a novel form of muscular dystrophy.     

Vitamin D levels in children with recurrent tonsillitis

Aim

Although recurrent tonsillitis can be the consequence of defects in immune system, the exact etiology of recurrent tonsillitis is not clear. In this study, our aim was to determine the serum vitamin D levels and vitamin D receptor polymorphism among children undergone tonsillectomy due to the recurrent tonsillitis.

Methods

A 106 children undergone tonsillectomy due to recurrent tonsillitis and a 127 healthy children aging between 2 and 12 years were enrolled in this study, to determine serum 25-hydroxyvitamin D level and vitamin D receptor gene polymorphisms (Apa1, Taq 1, fok1). Serum vitamin D level was measured with ELISA (nmol/L) and receptor gene polymorphism was determined by PCR. Vitamin D serum level below 80 nmol/L was accepted as insufficient.

Results

The average serum vitamin D level was 176 ± 79 nmol/L in recurrent tonsillitis group and 193 ± 56 nmol/L in control group. There was no significant difference between the groups (p = 0.13). In recurrent tonsillitis group, 18% (n = 15) of children had their serum vitamin D levels below 80 nmol/L. The vitamin D receptor gene polymorphism (APA1, TAQ 1, FOK 1) in each group was compared (AA, Aa, aa, TT, Tt, tt, FF, Ff, ff). There was no significant difference between the two groups. The vitamin D serum levels and receptor sub-genotypes are also compared, and there was no significant difference between the groups.

Conclusion

There is no difference between the serum vitamin D level and receptor gene polymorphism among children with recurrent tonsillitis and healthy children. But vitamin D insufficiency is more prevalent in children with recurrent tonsillitis group (18%).     

Oral delivery system prolongs blood circulation of docetaxel nanocapsules via lymphatic absorption

An original oral formulation of docetaxel nanocapsules (NCs) embedded in microparticles elicited in rats a higher bioavailability compared with the i.v. administration of the commercial docetaxel solution, Taxotere. In the present study, various animal studies were designed to elucidate the absorption process of docetaxel from such a delivery system. Again, the docetaxel NC formulation elicited a marked enhanced absorption compared with oral Taxotere in minipigs, resulting in relative bioavailability and C_max values 10- and 8.4-fold higher, respectively, confirming the previous rat study results. It was revealed that orally absorbed NCs altered the elimination and distribution of docetaxel, as shown in the organ biodistribution rat study, due to their reinforced coating, while transiting through the enterocytes by surface adsorption of apoproteins and phospholipids. These findings were demonstrated by the cryogenic-temperature transmission electron microscopy results and confirmed by the use of a chylomicron flow blocker, cycloheximide, that prevented the oral absorption of docetaxel from the NC formulation in an independent pharmacokinetic study. The lipoproteinated NCs reduced the docetaxel release in plasma and its distribution among the organs. The improved anticancer activity compared with i.v. Taxotere, observed in the metastatic lung cancer model in Severe Combined Immune Deficiency-beige (SCID-bg) mice, should be attributed to the extravasation effect, leading to the lipoproteinated NC accumulation in lung tumors, where they exert a significant therapeutic action. To the best of our knowledge, no study has reported that the absorption of NCs was mediated by a lymphatic process and reinforced during their transit.Docetaxel is widely used for lung cancer treatment, and its i.v. administration is often associated with acute hypersensitive reactions owing to the presence of polysorbate 80 in the formulation that is needed for drug solubilization (1, 2). Docetaxel also exhibits low and variable oral bioavailability due to the active efflux by the Permeability-Glycoprotein (P-gp) pump and to CYP3A4 gut metabolism (3). Thus, intensive efforts are being invested in the design of novel oral formulations of docetaxel, either combined with P-gp or CYP3A4 inhibitors (4, 5) or without such inhibitors (6). Most of these studies emphasize the absence of ethanol and polysorbate and the opportunity to investigate more schedule-intensive treatment regimens as major advantages (7). The clinical rationale behind such a trend is that shorter schedules result in more frequent exposure of docetaxel to tumor cells, whereas lower maximum plasma levels are reached, thus reducing the incidence of severe side effects (8). It should be emphasized that all of the formulations improved the oral bioavailability of docetaxel compared with Taxotere but still remain well below the absolute bioavailability elicited by the same dose of docetaxel injected i.v.We developed a unique polysorbate-free oral delivery system of docetaxel nanocapsules (NCs) embedded in gastro-resistant microparticles (MPs). Recently, we reported that the oral delivery of docetaxel NCs to rats elicited a higher bioavailability compared with the i.v. or oral administration of Taxotere (9). These unexpected results could only be explained if the pharmacokinetics of docetaxel had been modified (9). In this study, the drug absorption of the selected poly(dl-lactide-coglycolide) (PLGA) formulation was also investigated following oral administration to minipigs to verify if animal size might affect the oral bioavailability improvement observed in rats. Then, the in vivo efficacy of oral docetaxel NCs was investigated in mice using a metastatic lung cancer model as an additional milestone toward clinical trials. In addition, docetaxel organ biodistribution of the oral microparticulate formulation was investigated and compared with an oral solution of Taxotere, which had been combined with blank NCs embedded in MPs or i.v.-administered solutions of either docetaxel NCs or Taxotere alone. In addition, Lipiodol NCs were prepared and monitored by cryogenic-temperature transmission electron microscopy (cryo-TEM) following oral absorption of these NCs embedded in the MPs and respective controls in rats. Finally, to validate the results of the cryo-TEM, a third pharmacokinetic study of oral absorption of docetaxel-loaded nanoparticles (NPs) embedded in MPs was carried out in the absence and presence of cycloheximide, a protein synthesis inhibitor known to inhibit the secretion of chylomicrons from the enterocyte (10).