Alendronate PLGA microspheres with high loading efficiency for dental applications

Purpose: Alendronate sodium, used systemically as a bone protective agent, proved to also be effective locally in various dental bone applications. Development of alendronate-loaded microspheres with high loading efficiency for such applications would be greatly challenged by the hydrophilicity and low MW of the drug. The aim of this study was to incorporate alendronate sodium, into poly (lactide-co-glycolide) (PLGA) microspheres (MS) with high loading efficiency.

Methods: Three multiple emulsion methods: water-in-oil-in-water (W/O/W), water-in-oil-in-oil (W/O₁/O₂) and solid-in-oil-in-oil (S/O₁/O₂) were tested. In addition to entrapment efficiency, MS were characterized for surface morphology, particle size, in vitro drug release and in vitro degradation of the polymer matrix. Alendronate microspheres with maximum drug loading and good overall in vitro performance were obtained using the W/O₁/O₂ emulsion technique.

Results: Drug release from the microspheres exhibited a triphasic release pattern over a period of 13 days, the last fast release phase being associated with more rapid degradation of the PLGA matrix.

Conclusions: Biocompatible, biodegradable PLGA microspheres incorporating alendronate sodium with high loading efficiency obtained in this study may offer promise as a delivery system for bisphosphonates in dental and probably other clinical applications.     

How much can carpus rotate axially? An in vivo study

BACKGROUND: Supination and pronation movements occur primarily at the forearm though are possible at the wrist joint too. The axial rotation of the wrist also called the radiometacarpal rotation has been quantified but for its passive range which may never occur during the day-to-day routine activities. It is normally not possible for the wrist joint to rotate axially in an active manner. However, voluntary effort to rotate the forearm while keeping the hand fixed on a custom designed device is able to provide active rotation of the wrist which occurs in a manner similar to that occurring during the daily routine activities. METHODS: The present study measured axial rotation of the wrist in 20 asymptomatic volunteers who had axial CT done of their wrist with elbow in 10-30 degrees flexion and forearm positioned parallel to the long axis of the table with thumb pointing up towards the roof. The examination was repeated twice while the subject actively tried to supinate and pronate the forearm against the fixed hand and the metacarpals using maximum voluntary effort on a custom designed positioning device. FINDINGS: The mean radiometacarpal supination and pronation were 17.15 degrees (SD 7.9) and 17.0 degrees (SD 10) respectively. The movement was found to occur predominantly at midcarpal joint with radiocarpal joint contributing only 18% to supination and 31% to pronation. INTERPRETATION: The radiometacarpal rotation has a crucial bearing in the development of the wrist prostheses. The design of the prostheses should consider accommodating axial movements that occur in the carpus during the activities of daily living.     

Differential expression of T-helper cytokines in the peritoneal fluid of women with normal ovarian cycle compared with women with chronic anovulation

BACKGROUND: Estrogen and progesterone immunoregulate the genital environment by expression of cytokines and growth factors. OBJECTIVE: To investigate the pattern of expression of T-helper cytokines during the ovarian cycle compared with women with chronic anovulation resistant to clomiphene citrate. HYPOTHESIS: Expression of T-helper cytokines in women with chronic anovulation may be different from the pattern in women with a normal ovarian cycle. METHODS: We evaluated 31 infertile women having laparoscopy for evaluation of tubal patency and evidence of ovulation in two groups during (a) the luteal phase (17 women) and (b) the follicular phase (14 women). A third group was composed of 14 women with polycystic ovarian syndrome, but they were resistant to clomiphene citrate for induction of ovulation and had laparoscopic ovarian cautery. Peritoneal fluid was collected during laparoscopy. Estimation of T-helper cytokine interleukin (IL)-2, tumor necrosis factor (TNF)-alpha, IL-4 and IL-6 in serum, peritoneal fluid and culture of the peritoneal mononuclear cells was performed by ELISA. Serum luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, estradiol and progesterone were evaluated by the Vidas Parametric System. RESULTS: The LH : FSH ratio was significantly higher in the women with polycystic ovaries than in the ovulatory groups. IL-2 and IFN-gamma were more highly expressed in the follicular phase but the T-helper 2 cytokines IL-4 and IL-6 predominated in the luteal phase, serum, peritoneal fluid and culture of the peritoneal mononuclear cells. From the follicular to the mid-luteal phase, IL-6 increased three to fivefold in the serum and peritoneal fluid, but there was low expression with anovulation. CONCLUSIONS: The peritoneal fluid levels of IL-4 and IL-6 are higher in the luteal phase. Low IL-6 levels in chronic anovulation may be a marker of resistance to clomiphene citrate.     

Brain delivery of HIV protease inhibitors

To overcome the problems of peptidomimetic drug delivery to the specific organs, the use of dihydropyridine <--> pyridinium chemical delivery systems to deliver peptides to the brain is considered in this work. An HIV protease inhibitor lead compound; KNI 279 was selected for the study. The N-alkylated dihydroisoquinoline derivatives of KNI-279 were synthesized and tested for their ability to be oxidized by brain homogenate and showed good results with reasonable half-life times specially for the N-alkoxycarbonyl-methyl derivative 8. The in-vivo distribution of compound 8 proved the brain delivery and locked in property of HIV PR inhibitors in the brain. All the prepared compounds (both quaternary and dihydro derivatives) showed between 51 and 86 % HIV PR inhibitory activity compared to the parent compound.     

Increased expression of pro-inflammatory cytokines in placentas of women undergoing spontaneous preterm delivery or premature rupture of membranes

PROBLEM: The objective of this study was to determine the levels of cytokines in the placentas of women undergoing preterm delivery (PTD) or premature rupture of membranes (PROM) as compared with women undergoing normal delivery at term. METHOD OF STUDY: Placentas were obtained from 30 subjects with spontaneous PTD, 30 women with PROM and 30 women with a history of normal delivery at term. Levels of interleukin (IL)-2, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, TNF-beta, IL-4, IL-5, IL-6 and IL-10 and IL-12 were estimated by ELISA in detergent lysates of placentas from the subjects. RESULTS: We found significantly increased levels of the Th1 cytokines IL-2 and IFN gamma and of the Th1-inducing cytokine IL-12 in placentas from the PTD and PROM groups as compared with those delivering at term. In contrast, the levels of the Th2 cytokines IL-4, IL-6 and IL-10 were significantly higher in placentas from term pregnancy. CONCLUSIONS: These data support our observation of a pro-inflammatory cytokine bias in women with PTD and PROM.     

Gallstone ileus: An unusual cause of intestinal obstruction

Gallstone ileus is an infrequent cause of intestinal obstruction. It is typically the result of cholecystoduodenal fistula, computed tomography scan is the best modality for the diagnosis. Surgical removal of the gallstone is the pillar of treatment to relieve intestinal obstruction. We report the case of a 77-year-old male with features of a small bowel obstruction. Computed tomography scan of the abdomen showed pneumobilia, a cholecystoduodenal fistula, and small bowel obstruction features suspicious for gallstone ileus. The patient had a laparotomy and removal of two gallstones via an enterotomy without postoperative complications.