Optimization,in vitro release and toxicity evaluation of novel pH sensitive itaconic acid-g-poly(acrylamide)/sterculia gum semi-interpenetrating networks

BackgroundIn recent era, pH sensitive polymeric carriers that combines the materials engineering and medicine is gaining researcher’s attention as they maximizes drug concentration at site of absorption and reduces side effects for e.g. orally administered cetirizine HCl (CTZ HCl) upsets the stomach and furthermore shows high intestinal absorption. Thus, development of pH sensitive hydrogels with sufficient mechanical strength will be good candidate to address this issue.MethodsHere, we developed pH sensitive itaconic acid-g-poly(acrylamide)/sterculia gum (IA-g-poly(AM)/sterculia gum) semi-interpenetrating network (semi-IPN) by free radical polymerization technique for intestinal delivery of CTZ HCL.ResultsOptimized formulation (I5) with 6% w/w IA showed negligible swelling at pH 1.2, and maximum swelling at pH 7.4. Solid state characterization of optimized formulation showed successful development of semi-IPN structure and incorporation of drug without any noticeable drug-carrier interaction. In vitro release study showed biphasic pH dependent release of CTZ HCl, where initial burst release was observed at acidic pH followed by sustained release at basic pH. Acute oral toxicity and histopathological studies confirmed the non-toxic nature of IA-g-poly(AM)/sterculia gum.ConclusionConclusively, developed biocompatible semi-IPN hydrogels with sufficient pH sensitivity and mechanical strength could serve as a potential carrier for intestinal delivery of CTZ HCL to maximize its absorption and reduce side effects.Graphical abstract Supplementary InformationThe online version contains supplementary material available at 10.1007/s40199-021-00395-8.     

Evaluation of thyroglobulin expression in murine reproductive organs during pregnancy

Citation Moravej A, Jeddi‐Tehrani M, Salek‐Moghaddam AR, Dokouhaki P, Ghods R, Rabbani H, Kazemi‐Sefat GE, Shahbazi M, Zarnani AH. Evaluation of thyroglobulin expression in murine reproductive organs during pregnancy. Am J Reprod Immunol 2010; 64: 97–103 Problem In pregnant women with antithyroglobulin antibody, prevalence of abortion is 2–4 fold higher compared to normal controls. Direct effect of such harmful autoantibodies on female reproductive organs may serve a role in pregnancy loss. Method of study Expression of thyroglobulin in decidua, placenta, and ovary of pregnant Balb/c mice ((Balb/c×Balb/c and Balb/c×C57BL/6) during early, middle, and late stages of pregnancy was evaluated. Expression of thyroglobulin was investigated in these tissues by semi‐quantitative RT‐PCR. In addition, polyclonal antithyroglobulin antibody was produced, and expression of thyroglobulin protein in aforesaid tissues was evaluated by immunohistochemistry and dot‐blot analysis. Results The results showed that thyroglobulin message is not expressed in placenta, decidua, or ovary in any stages of pregnancy. The same results were obtained at the protein level. Conclusion It is likely that antithyroglobulin antibodies have no direct detrimental effect on such organs in patients with thyroid autoimmunity suffering from recurrent abortion.     

Effect of hormone administration on the sialylation and fucosylation of intestinal microvillus membranes of suckling rats

Cortisone, thyroxine, epidermal growth factor, or insulin were administered to 8-day-old rats for 4 days. In comparison to saline-injected controls, cortisone treatment: 1) lowered the sialic acid and raised the fucose content of the intestinal microvillus membranes, 2) increased [3H]fucose incorporation into these membranes, and 3) decreased the membrane binding of 125I-wheat germ agglutinin, while increasing the binding of 125I-ulex europeus agglutinin I and 125I-peanut agglutinin. Thyroxine treatment had similar effects on fucose content and 125I-ulex europeus agglutinin I binding, but did not alter [3H] fucose incorporation or sialic acid content. At the doses used, epidermal growth factor and insulin had no significant effects. The effect of cortisone treatment on sialic acid and fucose was commensurate with a 5- to 6-day acceleration of postnatal intestinal maturation. The changes in lectin binding, however, suggested qualitative differences between developmental and cortisone-induced membrane glycosylation. In addition, this study demonstrates significant quantitative and qualitative differences in the response of intestinal glycosylation to pharmacologic doses of the four hormones.     

Computed tomography in the diagnosis of primary tumors of the petrous bone

This paper constitutes an evaluation of 23 patients with signs and symptoms of 4 types of tumors: 6 congenital epidermoids, 3 cases of meningiomas presenting within the temporal bone, 2 cases of jugular fossa schwannomns, 3 cases of glomus tympanicum, and 9 selected cases of glomus jugulare tumors. Since these tumors occur insidiously and are located in an inaccessible region of the skull, they are usually not diagnosed until they reach considerable size and cause multiple cranial nerve deficits or intracranial complications. Assessment of these tumors and subsequent surgical management depend primarily on the preoperative radiographic findings. CT and dynamic CT study have proven to be extremely valuable and accurate in the diagnosis of these lesions. Epidermoids have a characteristic CT appearance. Dynamic CT is often helpful in differentiating glomus tumors from meningiomas and schwannomas. Involvement of the middle ear, labyrinth, intracranial, and extracranial components of these tumors can be best evaluated by CT. This paper places special emphasis on congenital cholcsteatoma (epidermoid) and draws relevant conclusions about the diagnostic work-up.     

Composite sequential grafts for femorocrural bypass reconstruction: experience with a modified technique

BACKGROUND: To evaluate the efficacy of a modification of the composite sequential femorocrural bypass graft that we adopted in 1985, a retrospective case-note study was undertaken. The grafts combined a prosthetic femoropopliteal section with a popliteal to crural section with autologous vein, linked via a common intermediate anastomosis sited on the above-knee popliteal artery. PATIENTS AND METHODS: Between 1985 and 2000, 68 grafts of this type were constructed in 65 patients with critical ischemia of the lower limb and insufficient autologous vein for construction of an all venous bypass. Reasons for insufficient long saphenous vein included previous lower limb bypass in 33 cases, phlebitis in 16 cases, venous hypoplasia in eight cases, and previous varicose vein surgery in seven cases. Distal anastomoses were carried out to the peroneal artery in 26 cases, the anterior tibial artery in 17 cases, the posterior tibial artery in 17 cases, and the pedal arteries in eight cases. Sources of vein included the long saphenous vein in 26 cases, the arm vein in 38 cases, and the short saphenous vein in two cases. In 22 limbs (32%), angiography had shown an occluded segment of above-knee popliteal artery, and in these cases, local popliteal disobliteration was performed to receive the composite anastomosis and to provide additional outflow. RESULTS: The 2-year cumulative primary patency, secondary patency, and limb salvage rates were 68%, 73%, and 75%, respectively. Localized popliteal disobliteration did not compromise graft patency (P =.07, with log-rank test). CONCLUSION: In the absence of sufficient autologous vein, patients needing bypass to crural arteries can be offered reconstruction with composite sequential grafting with satisfactory results. Furthermore, an occluded above-knee popliteal segment is not a contraindication for composite sequential bypass reconstruction.     

Intravenous administration of human umbilical cord blood reduces neurological deficit in the rat after traumatic brain injury

We measured the effect of treatment of traumatic brain injury (TBI) in the rat with human umbilical cord blood (HUCB) administered i.v.. HUCB cells were injected into the tail vein 24 h after TBI and the rats were sacrificed at day 28 after the treatment. The Rotarod test and the neurological severity score (NSS) were used to evaluate neurological function. The distribution of the donor cells in the brain, heart, lung, kidney, liver, spleen, bone marrow, and muscle were analyzed in recipient rats using immunohistochemical staining and laser confocal microscopy. HUCB cells injected i.v. significantly reduced motor and neurological deficits compared with control groups by day 28 after the treatment. The cells preferentially entered the brain and migrated into the parenchyma of the injured brain and expressed the neuronal markers, NeuN and MAP-2, and the astrocytic marker, GFAP. Some HUCB cells integrated into the vascular walls within the boundary zone of the injured area. Our data suggest that i.v. administration of HUCB may be useful in the treatment of TBI.     

Bioequivalence evaluation of two brands of gliclazide 80 mg tablets (Glyzide & Diamicron)--in healthy human volunteers

A randomized, two-way, crossover, bioequivalence study in 24 fasting, healthy, male volunteers was conducted to compare two brands of gliclazide 80 mg tablets, Glyzide (Julphar, UAE) as test and Diamicron (Servier Industries, France) as reference product. The study was performed at the International Pharmaceutical Research Centre (IPRC), in joint venture with Speciality Hospital, Amman, Jordan. The drug was administered with 240 ml of 20% glucose solution after a 10 h overnight fasting. After dosing, serial blood samples were collected for a period of 48 h. Plasma harvested from blood was analyzed for gliclazide by validated HPLC method. Various pharmacokinetic parameters including AUC(0-t), AUC(0- proportional, variant), C(max), T(max), T(1/2), and elimination rate constant were determined from plasma concentrations of both formulations. Statistical modules (ANOVA and 90% confidence intervals) were applied to AUC(0-t), AUC(0- proportional, variant), and C(max) for bioequivalence evaluation of the two brands which revealed no significant difference between them, and 90% CI fell within US FDA accepted bioequivalence range of 80-125%. Based on these statistical inferences, Glyzide was judged bioequivalent to Diamicron.     

Bioequivalence evaluation of two brands of metformin 500 mg tablets (Dialon & Glucophage)--in healthy human volunteers

A randomized, two-way, crossover study was conducted in 24 fasting, healthy, male volunteers to compare the bioavailability of two brands of metformin 500 mg tablets; Dialon (Julphar, UAE) as test and Glucophage (Lipha Pharmaceutical Industries, France) as reference product. The study was performed at the International Pharmaceutical Research Centre (IPRC), in joint venture with Al-Mowasah Hospital, Amman, Jordan. The drug was administered with 240 ml of water after a 10-h overnight fasting on two treatment days separated by 1-week washout period. After dosing, serial blood samples were collected for a period of 30 h. Plasma harvested from blood was analyzed for metformin by validated HPLC method with UV-visible detector capable to detect metformin in the range of 0.05-5.0 microg/ml with limit of quantitation of 0.05 microg/ml. Various pharmacokinetic parameters including AUC(0-t), AUC(0-proportional to), C(max), T(max), T(1/2), and lambda(Z) were determined from plasma concentrations of both formulations and found to be in good agreement with reported values. AUC(0-t), AUC(0-proportional to) and C(max) were tested for bioequivalence after log-transformation of data. No significant difference was found based on ANOVA; 90% confidence interval (97.9-110.8% for AUC(0-t), 97.4-110.7% for AUC(0-proportional to); 95.3-110.5% for C(max)) of test/reference ratio for these parameters were found within bioequivalence acceptance range of 80-125%. Based on these statistical inferences, it was concluded that Dialon is bioequivalent to Glucophage.