Evaluation of chondrocyte growth and function subjected to 21% and 6% oxygen levels.

In osteoarthritis, the metabolic activity of the chondrocytes is shifted toward a state where new matrix synthesis is outweighed by breakdown of matrix constituents. The result is degeneration and gradual loss of articular cartilage. Although osteoarthritis is frequently regarded as a non-inflammatory form of arthritis, considerable data implicates a role for pro-inflammatory cytokines in the cartilage destruction associated with osteoarthritis. The best studied pro-inflammatory cytokines in osteoarthritis are interleukin-1ß (IL-1ß), tumor necrosis factor-a (TNF-a), and interleukin-6 (IL-6). Since articular cartilage is not vascularized, it must rely on diffusion from the articular surface for nutrient and metabolic exchange. Consequently, the entire metabolism of the cell is geared towards operating at a low oxygen tension. In this study, chondrocytes were challenged with pro-inflammatory cytokines at 21% O2 and 6% O2. Chondrocyte proliferation, membrane integrity, oxidative stress, matrix metalloproteinase – 9 (MMP-9) and hypoxia inducible factor-1a (HIF-1a) production were measured. Our results showed that there was less of a decrease in cell number at 6% O2 compared to 21% O2 after they were challenged with pro-inflammatory cytokines. In addition, there was less of an increase in oxidative stress, membrane damage and MMP-9 production at 6% O2 compared to21% O2. The significance of this study represents the first attempt to replicate a diseased inflammatory environment characterized by an osteoarthritic joint in vitro and to examine these effects on the growth and stability of chondrocytes.

Morphometric evaluation of tissue-implant reaction associated with ALCAP and TCP bioceramics in vivo.

The purpose of this investigation was to correlate the thickness of the fibrous capsule and the various histological components surrounding aluminum-calcium phosphate (ALCAP) and tricalcium phosphate (TCP) bioceramics at the subcutaneous (sc) and intraperitoneal (ip) implantation sites. The rational of conducting this investigation is to further elucidate the mechanisms of tissue-implant interaction. Thirteen Sprague-Dawley adult male albino rats were randomly divided into three groups. Animals in groups I and II (n = 5/group) were implanted at both ip and sc implantation sites with either ALCAP or TCP ceramics, respectively. Animals in group III (n = 3) were not implanted and served as the intact control for the comparative purposes. At 90 days postimplantation, the animals in all groups were euthanized (Ketamine/Zylazane) and the fibrous tissue surrounding the ceramic devices was retrieved. After routine histological processing, sections (5 microm) of tissue was stained with hematoxylin and eosin (H&E) and evaluated using light microscopy. With the exception ofneutrophils, at both implantation sites, the fibrous tissues surrounding the TCP bioceramics demonstrated greater capsular thickness, more vascularity, and more macrophages, fibroblasts, and collagen than those surrounding the ALCAP ceramic. Data obtained from this investigation provided further insights into the differences in the tissue-implant responses of calcium-phosphate-based ceramics and the cellular composition of the fibrous tissue reaction found at sc and ip implantation sites.

Nodular hematopoiesis of the liver diagnosed by fine-needle aspiration cytology.

A case of tumor-like extramedullary hematopoiesis (EMH) of the liver diagnosed by fine-needle aspiration cytology guided by computer tomography (CT) is reported. The initial clinical diagnosis was metastatic carcinoma from an adrenal gland primary. Five other cases of tumor-like EMH diagnosed by FNA have been presented in the literature. In two of the cases, the primary clinical diagnosis was metastatic tumor. The most common location for tumor-like EMH is paravertebral and intrathoracic. Three such cases of paravertebral tumor-like EMH have been diagnosed by FNA. Nodular EMH can be found rarely in other organs as in the liver.

Accuracy of fine needle aspiration biopsy of the breast.

Fine needle aspiration biopsy (FNAB) has become a widely used and accepted procedure to detect benign and malignant lesions of the breast. In the past, highly invasive procedures were used in the investigation of suspect breast tumors. Surgical excision was the method of choice during this period often requiring hospitalization of the patient. However, the recent introduction of FNAB has allowed a less traumatic approach for such investigations. Due to pressures from Health Management Organizations (HMO's), FNAB is presently the method of choice allowing for decreased patient trauma, expense, and ability of the procedure to be performed on an outpatient basis. Although highly accepted by most clinicians, others suggest that FNAB should perform diagnostically at a level equivalent or higher than that obtainable by frozen tissue sectioning procedures. This study was designed to evaluate the diagnostic ability of FNAB. Four-hundred twenty-seven patients underwent FNAB during 1993-94 at the University of Mississippi Medical Center. Of those patients, two hundred thirty-seven also underwent corresponding surgical biopsies. Sensitivity (88%), specificity (96%), a false positive rate (4%), and a false negative rate (12%) were calculated from the data and reported. In conclusion, the diagnostic accuracy of FNAB of the breast determined in this study shows the significance of the procedure.

Abnormal cervical lesions in young adults.

The objective of this study is to determine the prevalence of cervical lesions in a population of young adults. This study took into account 897,900 pap smears kindly provided by the cytopathology division at the University of Mississippi Medical Center. These cases were subdivided into three different groups based on age. Group one represents the age population of 0-17, group two represents the age population of 18-34, and group three represents the age population of 35 and higher. Seven different parameters were evaluated in this study. These include negative: unsatisfactory, atypia, CIN I, CIN II, CIN III, and invasive carcinoma. Data obtained from this study suggests that cervical lesions among young teenagers were found to be significant and our observations recommend that this population be screened and evaluated on a regular basis. The results of this study conclude that cervical lesions are significant among young adults. This age group would benefit from education and routine screening. In addition early sexual activity, multiple partners, and infectious diseases were noted in cases with cervical cancer. This could be due to the high occurrences of SIL in young adults. Screening of this age group is highly recommended for those young adults at "high risk."

Reactive cell change in cervicovaginal smears.

Reactive cell change in cervicovaginal smears is a controversial issue. The most common criteria for reactive cell change include an increase in nuclear size, presence of nucleoli, binucleation, cytoplasmic vacuolization, and polychromasia. The purpose of this study is to define, as specifically as possible, the criteria of reactive cell change. Sixty-one cervicovaginal smears in a routine examination obtained during 1988 to 1994 were reviewed for this study. All cases had been diagnosed as reactive. Fifty-three of these were re-diagnosed as reactive and 8 cases were rediagnosed as negative. Inflammatory cells were present in 79% and organisms involvement such as Herpes, Trichomonas, Chlamydia, Gardnerella, and Candida were present in 23% percent. The smears were also evaluated for cellular arrangement, origin of the reactive cells, and presence of nucleoli. The majority of reactive cells were found in aggregates and were of metaplastic origin. Nucleoli were present in 85% of the cases. In all cases the most important criteria of reactive cell change were found to be aggregates of metaplastic cells with central nuclei containing nucleoli and a fine chromatin pattern, followed by the presence of organisms. Additionally, the majority of cases with a cytology diagnosis of reactive cell change had a squamous intraepithelial lesion on biopsy. In conclusion, this study suggests that follow-up Pap smears over a two year period may revert to normal in some of the cases.

The role of various biomedical polymers concentration on the adhesion rate and viability of monocyte and monocyte derived macrophages.

The relationship between various polymers used in surgical implantation and cellular response at that particular site has not been fully elucidated. The objective of this study was to investigate the effect of various biomedical polymers on the adherence and viability of monocyte and monocyte derived macrophages. The monocytes were isolated from human peripheral blood, biotin labeled and seeded at a density of 5 x 10(5) cells/well according to standard laboratory procedures. Cells were considered macrophages after remaining in culture for 24 hours. Cells were then plated in each microtiter well pretreated with various concentrations of (0.01, 0.1 and 1%) poly-1-valine (P-Val), Poly-L-Alanine (P-Ala), poly-glycine (P-Gly), poly-L-tryptophan (P-Trp), Poly-L-Asparagine (P-Asn) and buffered control. At the end of 3 hours, 2 and 7 days the viability and cell number of monocyte or monocyte derived macrophages were determined using an established assay (biotin-labeled-macrophages). Cell number was determined in control wells with known amounts of cell number, a standard curve was generated by plotting absorbance units versus cell number. The data from this experiment suggest that: (I) cell number and viability of monocytes and macrophages can be measured concurrently, for the first time, by the use of Alamar Blue methodology, and (II) monocytes and macrophages are capable of surviving on all concentrations (0.01, 0.1 and 1%) of polymers tested over a 7 day period. Information obtained from this study provided new insights on the interrelationship between commercially available polymers, dose effect, incubation time and the possible cell response during chronic inflammation at the site of implantation.

Quantitative analysis of the effect of surface impregnation with biomedical polymers on the proliferation rate of HeLa cells in culture.

The use of biomaterials in biological system was extensively conducted in an in vivo environments. This method limits the evaluation and imposes an obstacle for quantitative analysis of several parameters. The development of tissue culture techniques to evaluate the bioactivity of potential organic compounds alleviated these problems and provided a reliable prediction regarding the biocompatibility of biomaterials when compared with parallel animal testing. The objective of this study is to investigate the effect of various biomedical polymers on the adhesion rate of transformed HeLa cells as a model. The HeLa cells used in this study seeded by following our standard laboratory procedure. A total of 1.5 x 10(5) cells were plated in each of the pretreated wells with various concentrations of (0.01 0.1 and 1% wt/vol) polyvaline (P-Val), polyalanine (P-Ala), polytryptophan (P-Trp), polyasparagine (P-Asn), polyaspartate (P-Asp), poly glycine (P-Gly), and buffered control. At the end of 1,4, and 24 hours the cell viability was determined by hexoamindase activity. The data obtained from this study suggest that (I) the ease of adhesion of HeLa cells were in the following order: P-Val = P-Ala > P-Gly = P-Trp = P-Asp = P-Asn > Control, (II) the rate of HeLa cells spreading was strongly influenced by both incubation time and the polymer concentration, and (III) the surface attachment of HeLa to the polymer were demonstrated to vary depending on their chemical structure and level of microporosity. Thus, overall observation led us to conclude that the surface reactivity of polymer materials be always taken into account in discussing their biocompatibility in vivo.

Long-term sustained delivery of androgens by means of TCPL devices and the effect on high-density lipoprotein in castrated rams.

Several studies have established that conventional routes of androgens administration resulted in a decrease in high-density lipoprotein cholesterol (HDL-C), a major risk factor for coronary artery disease. The HDL-C response to the long-term sustained delivery of androgens by means of tricalcium phosphate-lysine implants (TCP-L) has not been investigated. Suffolk rams (40-57 kg) were used for this investigation. A total of 11 rams were castrated by elastrater rings at birth. At 7 months of age, these animals were randomly divided into three groups. Group 1 rams (n = 3) served as control group. Groups 2 (n = 4) and 3 rams (n = 4) were implanted subcutaneously into the axillary region with sterilized (ethylene oxide) TCP-L capsules, containing testosterone (T) and Dihydrotestosterone (DHT), respectively. Blood samples (5 ml) were collected from the experimental and control animals by jugular venipuncture weekly for 12 months. After blood samples were allowed to clot (12 hours), serum was separated by centrifugation and stored at -20 degrees C until analyzed. Circulating T and DHT levels were measured by solid-phase radioimmunoassay and HDL-C and protein by colorimetric method and lipoprotein fractions mobility by electrophoresis. The results demonstrated that after castration, the HDL-C concentrations increased significantly in all animals (P < .001). Sustained delivery of T (4-6 ng/ml) and DHT (1.5-2 ng/ml) produced a significant decrease in HDL-C (P < .001), in which was similar to HDL-C reductions seen when the animals were treated with DHT-TCPL (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of sustained delivery of danazol and antioxidants on lipoprotein profiles of adult female mice.

The specific objectives of this study were: (i) to investigate the relationship between Danazol alone or in combination with tocopherol acetate (TA) and lipoprotein profiles using adult female mice as a model, and (ii) to study the effect of sustained delivery of D+TA versus injections on the lipoprotein profiles. D was given (alone or in combination with TA) to adult female mice (n = 52) in levels of 2 and 6 ng for 4 weeks, and the morphological evaluation as well as serum lipoprotein was analyzed. The results showed that the use of D at dosages ranging between 2-6 ng alone or in combination with physiological dose of TA induced suppression of ovarian weight, presumably by inhibiting gonadotropin secretion, and enlargement of uterine hornes. Histopathological evaluation demonstrated that the uterus of mice in every group that received D increased in weight 5 to 7 fold as compared with the sham operated controls. Uterine enlargement was characterized by a thickened stroma and muscular wall and by a heightened columnar epithelium. Serum lipoprotein analysis revealed that D or D+TA treatment decreased total cholesterol by a range of 3-9%, apo A-1 by 3-11%, apo A-11 by 2-13% and HDL-Chol fell by 6-53%. In contrast, LDL-Chol increased by 2-12% in all animals treated with D or D+TA. Lipoprotein electrophoresis indicated an elevated beta-lipoprotein band in the animals treated with D and no significant change observed in D+TA treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Pathophysiological evaluation associated with sustained delivery of danazol and dihydrotestosterone in adult male rodents.

The objective of this investigation was to evaluate histologically and pathologically the effect of long-term sustained release of D and DHT on the reproductive system of male rats. A total of 120 Sprague-Dawley male albino rats were distributed equally into three groups. Two CDD, one nonimpregnated and the other impregnated with PLA, were implanted in each rat in groups I and II. Capsules implanted in group I rats were loaded with 20 mg DHT and 20 mg D each. Group II rats were implanted with two empty capsules (sham group), and group III animals served as unimplanted controls. Blood samples were withdrawn weekly via tail artery from all animals. Eight rats from each group were euthanized at the end of the one, three, six, nine, and twelve months following the implantation of the devices. No significant changes in the weights of vital (spleen, kidneys, heart, adrenals, lungs) organs of rats were observed among any of the three different groups. Vas deferens and epididymal fluid were devoid of normal spermatozoa within three months of implanting the D+DHT containing devices. Testes weights decreased significantly in the rats implanted with CDD containing D+DHT and the seminiferous tubules became oligospermic after one month and azoospermic after three months.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of different biomaterials on adhesion of nontransformed buccal epithelial cells.

The specific objective of this study was to investigate the effect of various biomedical polymers on the adhesion rate of buccal epithelial cells (BEC) as a model for biocompatibility. The BEC in this study were isolated, biotin labeled and seeded by following standard laboratory procedures. A total of 2.5 x 10(5) cells was plated in each microtiter-well pretreated with various concentrations of (0.01, 0.10 and 1% wt/vol) poly-L-valanine (P-Val), poly-L-alanine (P-Ala), poly-glycine (P-Gly), poly-L-tryptophan (P-Trp), poly-L-asparagine (P-Asn) and buffered control. At the end of 1, 4, and 24 hours the assay was developed by utilizing avidin-horseradish peroxidase and o-phenylenediamine dihydrochloride as substrate to measure biotin-labeled-BEC. Cell number was then determined using a standard curve prepared by using known BEC number vs. absorbance units. The data from this study suggest that: (I) the ease of adhesion of BEC was in the following order: P-Val > P-Gly = P-Trp = P-Ala > P-Asn > P-Asp = Control, (II) the rate of BEC spreading was strongly influenced by both incubation time and the polymer concentration, (III) the surface attachment of BEC to the polymer were demonstrated to vary depending on their chemical structure and level of microporosity. Thus, overall observation led us to conclude that the surface reactivity of polymer materials must always be taken into account in discussing their biocompatibility in vivo.

Successful antidote of multiple lethal infections using sustained delivery of difluoromethylornithine by means of ceramic drug delivery devices.

The objectives of this study were (1) to cure multiple infections of trypanosomiasis in rats by the sustained release of DFMO from biodegradable tricalcium phosphate (TCP) and aluminum-calcium-phosphorous oxide (ALCAP) delivery systems, and (2) to determine if the side effects associated with oral administration of DFMO can be avoided by using TCP and ALCAP capsules. Sixty-eight SD male albino rats (235-270 g) were divided randomly into five groups. Each rat in group I (n = 16) was implanted subcutaneously (s.c.) with four TCP capsules (two large TCP (L-TCP), one PLA-impregnated large TCP (IL-TCP) and one thin TCP capsule (TN-TCP)). Rats in group II (n = 16) were implanted s.c. with four ALCAP ceramics (two large ALCAP (L-ALCAP), one PLA-impregnated large ALCAP (IL-ALCAP) and one thin ALCAP capsule (TN-ALCAP)). Rats in groups III (n = 16), IV (n = 4) and V (n = 16) were left without implants. Rats in group III (n = 16) were given 4% (w/v) DFMO (pH 7) in drinking water at the day of inoculation and continued up to 7 days postinoculation. Rats in group IV (n = 4) served as a nontreated group. Rats in group V (n = 16) served as normal controls. The results showed that all rats implanted with with TCP or ALCAP implants had no intoxications symptoms or side effects such as diarrhea during the treatment period. In contrast, rats given DFMO in drinking water exhibited foul-smelling diarrhea during the treatment period. Microscopic evaluation of blood smears collected from rats receiving DFMO chemotherapy showed an occasional or limited number of stumpy shape (SS) trypanosomes. This study suggests that (1) ceramic drug delivery systems are capable of delivering DFMO in a sustained manner for two months, and were able to cure repeated infections of trypanosomiasis; (2) the use of ceramic implants avoided widely fluctuating, irregular levels of DFMO in the body by keeping sustained levels above minimal effective concentrations; (3) ceramic drug delivery systems provide a pharmacological potentiality for drugs such as DFMO which have been withheld from the market because of severe side effects when administered using conventional methods of drug administration; and (4) DFMO-filled ceramic devices can be implanted subcutaneously in animals that face a threat of lethal protozoal infections in highly infested areas of the world.

Sustained release of progesterone and estradiol on adult female rats by ceramic delivery devices.

The present study was undertaken with the purpose of investigating the effectiveness of CDS implants to deliver progesterone (P) and estradiol (E) in a sustained levels for long duration using adult female rats as a model. A total of 128 CDS implants, each having a final fired density of 1.88 +/- S.D. 0.17 g/cm3, were fabricated by using standard laboratory procedure. A total of 80 CD-female rats were randomly divided into five equal groups. Rats in groups II, III and IV and V were implanted with capsules containing 100 mg P, 5 mg E, 100 mg P plus 5 mg E, and 100 mg P plus 10 mg E. Group I animals were left without implants and served as controls. At the end of 2,4, 6 and 10 weeks postimplantation four rats from each group were euthanized and the reproductive organs were collected and the CDS devices were retrieved. The total amount of P and E left within the devices was determined spectrophotometrically. Data obtained indicates that a sustained rather constant release of P and E during the entire investigation. Steroid delivery rates from the CDS implants in groups II and III and IV differed significantly (P,0.05) for the 10 week period of the experiment. The results show that the rate of E released from the CDS implants was directly proportional to the amount of steroid placed initially in the reservoir.(ABSTRACT TRUNCATED AT 250 WORDS)

Controlled release of hydrophilic compounds by resorbable and biodegradable ceramic drug delivery devices.

Hydroxyapatite (HA), aluminum-calcium-phosphorous oxide (ALCAP), bone meal (BM), and tricalcium phosphate (TCP) ceramic implants are biodegradable and nontoxic to the host. The purpose of this study was to investigate the capability of these ceramics to deliver the catecholamine, epinephrine (EPI) in a sustained and controlled manner. The ceramic powder (less than 38 um particle size) was prepared in our laboratory using standard procedures. Sixteen cylinders were prepared (1 g each) from each of the four ceramic materials. All cylinders were pressed at a compression load of 615 Kg and sintered for 36 hours. ALCAP (group I) and BM (group II) cylinders were sintered at 1400 degrees C and HA (group III) and TCP (group IV) ceramic capsules were sintered at 1150 degrees C. Three capsules from each group were loaded with 30 mg EPI. Capsules containing EPI and control (empty) capsules were each suspended in a serum bottle containing 100 ml of phosphate buffered saline (pH 7.4). The amount of EPI released from each capsule was determined by spectrophotometric methods. Data collected from this study showed that the rate of release of EPI from ALCAP, HA, BM and TCP was 6.14 +/- 0.3 3.55 +/- 0.29, 2.07 +/- 0.26 and 1.17 +/- 0.04 mg/day, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of ceramic drug delivery devices: the effect of various temperature of incubation on the delivery of biologicals.

The objectives of this study are: (i) to determine the effect of temperature on the release rate of steroids and proteins from ceramic drug delivery devices (CDDD), and (ii) to examine the effect of polylactic acid (PLA) impregnation of tricalcium phosphate (TCP), and alumino-calcium-phosphorous oxide (ALCAP) ceramic capsules on the release of small and large molecular weight compounds, and (iii) to investigate the interaction of molecular weight and various incubation temperatures (25, 37 and 50 degrees C) on the rate of delivery from CDDD. The CDDD were prepared using standard laboratory protocols. Eight of 16 ALCAP and TCP ceramic capsules were impregnated with PLA and the remainder fabricated without PLA. Fourteen ceramic capsules were loaded with either 40 mg of testosterone or 40 mg of bovine serum albumin (BSA), and nothing was added to the two remaining capsules. All capsules were then sealed at both ends with Dow Corning Type A Silastic Medical Adhesive. Single capsules were suspended in serum bottles containing either 100 ml of 50% wt/vol aqueous ethanol solution (steroid-containing capsules) or 100 ml of phosphate buffered saline (pH 7.4) (protein-containing capsules). The bottles were then placed in one of three metabolic shaker baths that had been previously adjusted at 25, 37, or 50 degrees C and were oscillating at a frequency of 100 rpm. Testosterone release was measured spectrophotometrically at 245 nm and BSA by a colorimetric procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo delivery of estradiol from ceramic drug delivery devices.

Ceramic drug delivery systems (CDS) are capable of delivering a wide variety of chemicals and/or biologicals directly into the systemic circulation in a continuous manner over long intervals with minimum risk to the recipient. The objectives of the present study were: (i) to determine the capability of tricalcium phosphate (TCP) capsules to deliver estradiol (E) in a sustained manner into the circulation of intact adult male rats, and (ii) to investigate the physiological responses associated with the presence of constant levels of estradiol in adult male rats. Microcrystals, particle size of less than 38 um, of TCP powder were prepared using standard procedures. TCP capsules with an outer diameter of 0.8 cm and an inner diameter of 0.4 cm were prepared by compressing calcined materials in a cylindrical dye at a compression load of 700 Kg. The ceramic capsules had a final density of 1.82 +/- 0.03 gm/cm3. A total of 54 adult male rats were divided into three groups of 18. Each rat in group I was implanted intraperitoneally with 2 CDS, one TCP capsule impregnated with polylactic acid (PLA) and the second nonimpregnated TCP capsule. Each capsule contained 40 mg of E. Animals in group II were implanted with two similar capsules without E (shams) and group III animals which served as intact controls were not fitted with CDS. Eight rats from each group were euthanized 2, 4, or 6 months following CDS implantation. Ceramic capsules were retrieved from the euthanized animals and the amount of E left within the ceramic was determined.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of various testosterone concentrations released from ceramic delivery systems on the circulating hormone levels of adult castrated rams.

Ceramic delivery systems (CDS) have been found to be useful carriers for chemical and biological materials allowing a constant release of these materials over prolonged periods of time. We reasoned that testosterone (TE) filled CDS could be utilized in the long-term treatment of androgen deficient patients. The specific objective of this study was to investigate the ability of CDS to deliver TE at a sustained level for 90 days using castrated adult rams as a model. Ceramic capsules were fabricated to a final density of 1.72 +/- 0.02 gm/cm3. The sintered capsules were loaded with either 440 mg or 700 mg TE and then sealed at both ends and subsequently sterilized by exposure to ethylene oxide for 24 hours. The TE-filled CDS were then implanted subcutaneously, under the forelimb of yearling rams (body weight; 30-42 Kg). Radiographs of implanted ceramics one week after implantation indicated that the capsules were intact and unaltered. The passage of TE through CDS capsules started within 4 days after implantation. An initial high release of the steroid was noted in all experimental animals which was maintained for up to 12 days post-implantation. After the initial high rate of release the serum concentration of TE remained constant at about 0.35 nM/ml in rams implanted with CDS containing a high TE dose and serum concentrations of approximately 0.21 nM/ml were observed in rams treated with the low dose capsules. There was no significant change in body weight gain between the experimental and castrated control rams.(ABSTRACT TRUNCATED AT 250 WORDS)

Tricalcium phosphate amino acid capsules as a drug delivery system for steroid hormones.

Several researchers have reported that there are drawbacks in using the current pharmacotherapeutic procedure for the treatment of endocrine insufficiency. Furthermore, such drugs have to be taken on a lifelong basis. Also, long term exposure to drugs seems to be necessary in the treatment of the most common endocrine disorders. Thus, the traditional routes of administration expose the body constantly to large fluctuating levels of drugs. This study presents a possible alternative route of administering the drugs for the treatment of the aforementioned cases. Ceramics, such as, tricalcium phosphate (TCP) have been used extensively in the dental and orthopedic fields. To date, the use of compressed TCP ceramic capsules as drug delivery systems has not been investigated. The objective of this study is to investigate the capability of calcined TCP amino acid-steroid matrix to deliver progesterone (P), in a sustained manner. Microcrystals of TCP were prepared by following standard laboratory procedures. Three different amino acids (cysteine, proline, and lysine) were incorporated (individually or in combination form) into the TCP matrix. Each matrix contained 100 mg of P and the homogeneous material was compressed at 5000 Kg compression load using a French Pressure Cell. The total amount of steroid released was monitored spectrophotometrically. The results of this study suggest that: (i) TCP- amino acid-steroid composites can be used to deliver steroids in a sustained manner. (ii) The amount of steroid released from the matrix system was found to be dependent upon the physiochemical characteristics of the amino acids.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term delivery of testosterone by ALCAP ceramic implants in rats.

The capability of ALCAP ceramic drug-delivery implantable devices to release testosterone for 12 months was investigated. A total of 120 Sprague-Dawley male albino rats were distributed equally into three groups. Two ALCAP capsules, one nonimpregnated and the other impregnated with polylactic acid (PLA) were implanted into each rat in Groups I and II. Capsules implanted into Group I rats were loaded with 40 mg testosterone (T) each. Group II rats were implanted with two empty capsules (sham group), and Group III animals served as unimplanted controls. Eight rats from each group were euthanized at the end of 1, 3, 6, 9, and 12 months following the implantation of the ceramics. No significant changes in the weights of vital organs of rats were observed between any of the three different groups. Vas deferens and epididymal fluid were devoid of normal spermatozoa within 3 months of implanting the steroid-containing ceramics. Testes and epididymis weights decreased significantly in the rats implanted with ALCAP ceramics containing steroid, and the seminiferous tubules became oligospermic after 1 month and azoospermic after 3 months. Circulating levels of both LH and FSH hormones were suppressed in experimental rats. Serum T level was lower than the control but showed no significant difference in comparison to control rats. The data collected in this study suggest that: (a) ALCAP ceramic capsules are capable of delivering T in a sustained manner for 12 months; (b) T delivered by ALCAP capsules can be used effectively to regulate spermatogenesis in rats.