Suleyman Bacinoglu

Development of starch based mucoadhesive vaginal drug delivery systems for application in veterinary medicine.

The aim of this study was to prepare and evaluate the mucoadhesive, biocompatible and biodegradable progesterone containing vaginal tablets based on modified starch copolymers for the estrus synchronization of ewes. Starch-graft-poly(acrylic acid) copolymers (S-g-PAA) were synthesized and characterized. The vaginal tablets were fabricated with S-g-PAA and their equilibrium swelling degree (Qe) and matrix erosion (ME%) were determined in lactate buffer solution. In vitro, mucoadhesive properties of the tablets were investigated by using ewe vaginal mucosa and in vivo residence time were also investigated. In vitro and in vivo progesterone release profiles from the tablets were compared with two commercial products. Tablet formulation containing wheat starch based grafted copolymer (WS-g-PAA)gc indicated promising results and might be convenient as an alternative product to the commercial products in veterinary medicine.

Lambing rates and litter size following carazolol administration prior to insemination in Kivircik ewes.

The effect of carazolol on the ease of penetrating the cervix during artificial insemination, lambing rate and litter size was studied using 1.5-4.0-year old Kivircik ewes in an incomplete 3 x 2 x 2 experimental design. All of the ewes in this study were synchronized for oestrus by insertion of a progesterone impregnated vaginal sponge for 12 days and administration of 400 IU PMSG at sponge withdrawal. Three methods of service were compared: natural service, artificial insemination (AI) with fresh semen, or AI with frozen semen. Two times of insemination (fixed time AI versus AI at observed oestrus) were compared on the fresh and frozen AI treatments. The absence (control) or use of carazolol (carazolol; 0.5mg/ewe i.m. 30 min before mating) was the third factor in the design and penetration of the cervix by the insemination pipette was assessed as shallow (<10mm), middle (10-20mm) or deep (>20mm). Natural service ewes were only mated at observed oestrus. Consequently, the factorial design was incomplete and there were a total of 10 treatments each represented by 30 ewes. Natural service resulted in a significantly (P<0.05) higher lambing rate and litter size (86%; 2.0+/-0.05 lambs/ewe) than AI using fresh (65%; 1.6+/-0.1 lambs/ewe) or frozen (40%; 1.4+/-0.14 lambs/ewe) semen. For AI animals the lambing rate and litter size were not significantly different when service was at a fixed time (50%; 1.5+/-0.12 lambs/ewe) or at observed oestrus (56%; 1.5+/-0.12 lambs/ewe). Carazolol did not permit complete cervical penetration in any ewe. Deep penetration of the cervix at AI was achieved in 33% of untreated (control) and 48% of carazolol treated ewes (P<0.05). However, the proportion of ewes in which penetration of the cervix and semen deposition was greater than shallow was similar for control (82%) and carazolol (85%), and lambing rate and litter size were similar for both treatments. Over the three service methods, the lambing rate was 56% for control and 63% for carazolol (NS) and litter size was similar for both treatments. It was concluded that the carazolol treatment used prior to natural mating or AI in this experiment did not improve lambing rate or litter size in Kivircik ewes.

The effects of the thiolation with thioglycolic acid and l-cysteine on the mucoadhesion properties of the starch-graft-poly(acrylic acid)

The aim of this study is to investigate the effects of the thiolation on the mucoadhesion characteristics of the gelatinized and crosslinked wheat starch-graft-poly(acrylic acid) [(WS-g-PAA)gc] for potential use in drug delivery via vaginal route. Thiolation of (WS-g-PAA)gc was first time realized using l-cysteine hydrochloride monohydrate (CyS) and thioglycolic acid (TGA). These conjugates [(WS-g-PAA)gcth] were characterized using FTIR. The free SH group, mucoadhesion, cytotoxicity characteristics and the mechanism of the thiolation were also evaluated. To obtain fundamental data for possible application such as drug carrier, in vitro and in vivo progesterone release profiles from the mucoadhesive tablet formulations were also determined. The results showed that, vaginal tablet containing (WS-g-PAA)gc-TGA, which has not contain free SH groups in its structure, displays higher mucoadhesion than (WS-g-PAA)gc and (WS-g-PAA)gc-CyS. This tablet formulation can also be used as a drug carrier in vaginal applications.

Evaluation of short estrus synchronization methods in dairy cows

In the present study, two new short estrus synchronization methods have been developed for lactating dairy cows. The study was completed in three consecutive phases. In experiment (Exp) 1, 32 cows, that were not detected in estrus since calving between the 50th and 84th post-partum days, were treated with PGF2alpha (PGF, d-cloprostenol, 0.150 mg), estradiol propionate (EP, 2mg) and GnRH (lecirelina, 50 microg) at 24h intervals, respectively, and timed artificial insemination (TAI) was performed 48 h after PGF. Different from Exp 1, EP and GnRH were given at 48 and 60 h, respectively after PGF in Exp 2 (n=20), instead of 24 and 48 h. Ovulations were investigated by ultrasound for 7 days starting from the day of PGF treatment, and ovulation rates were compared with the ones obtained in Exp 1. In Exp 3, cows were given the same treatments as Exp 2, but treatments started at certain estrus stages. Cows detected in estrus and with a confirmed ovulation (n=27) after the second PGF given 11 days apart were assigned to three treatment groups. Treatment was initiated at Day 3 (group metestrus, n=9), Day 12 (group diestrus, n=9) and Day 18 (group proestrus, n=9) after ovulation. All cows included in Exp 3 were TAI between 16 and 20 h after GnRH treatment. In Exp 2 and 3, blood samples were obtained once every 2 days, starting from Day 0 to the 10th day after GnRH injection, and once every 4 days between the 10th and the 22nd days after GnRH to examine post-treatment luteal development. During the study, animals exhibiting natural estrus were inseminated and served as controls (n=85). The rate of estrus was found to be significantly higher in cows with an active corpus luteum (CL) at the start of Exp 1 (72.7% vs. 30.0%, P<0.05) and the pregnancy rate tended to be higher than cows without an active CL (40.9% vs. 10.0%, P=0.08). Compared to those in Exp 1, cows in Exp 2 had higher rates of synchronized ovulation (94.1% vs. 59.1%, P=0.013). In Exp 3, estrus (P<0.001) and pregnancy rates (P=0.01) were found to be significantly higher in cows in the proestrus group than in those in the metestrus group. Comparable pregnancy rates were obtained from the first and second inseminations in Exp 1 and 3 with results from those inseminated at natural estrus (P>0.05). It was concluded from the study that the treatment in Exp 1 and 3 could result in comparable pregnancy rates after timed AI of lactating dairy cows at random stages of the estrus cycle relating to those inseminated at natural estrus, but the stage of the estrus cycle can have significant effects on pregnancy rates.