Intraoperative parathyroid hormone monitoring fails to detect double parathyroid adenomas: a 2-institution experience.

BACKGROUND: We hypothesized that intraoperative parathyroid hormone monitoring (IOPTH) reliably would detect double parathyroid adenomas. METHODS: This was a retrospective study of 20 patients undergoing conventional parathyroidectomy with resection of exactly 2 abnormal glands. Full exploration was performed regardless of IOPTH values, which were measured after anesthetic induction and 5 and 10 minutes following removal of the first abnormal parathyroid gland. Failure to fall below 50% of baseline value by 10 minutes following resection of the first gland indicated the presence of multiglandular disease. RESULTS: All patients were cured. All excised glands were hypercellular on histology. Mean IOPTH values in 9 of the 20 patients with true negative results (noncurative decrease, another gland present) were 66% +/- 7% at 5 minutes and 83% +/- 15% at 10 minutes. The IOPTH values in 11 of the 20 patients with false positive results (curative decrease, another gland present) were 28% +/- 4% at 5 minutes and 18% +/- 2% at 10 minutes. The false positive rate of IOPTH was 55%. CONCLUSIONS: We found that IOPTH failed to reliably detect the presence of double parathyroid adenomas. These data suggest that caution should be exercised when terminating limited parathyroid exploration based on a curative fall in IOPTH values.

Serum thyroglobulin levels after thyroxine withdrawal in patients with low risk papillary thyroid carcinoma.

We hypothesized that elevated levels of serum thyroglobulin (Tg) are frequently found as the only index of residual neoplasm in patients with low-risk papillary thyroid carcinoma. The records of patients operated on for papillary thyroid carcinoma over a 2-year period were reviewed, and the patients were allocated to risk groups by a validated staging method that does not include Tg levels. Of the 35 patients who manifested a low-risk carcinoma, 9 (26%) exhibited elevated Tg concentrations (11-53 ng/mL) during thyroxine withdrawal after therapies, while clinical, scintigraphic, and radiographic studies at least 1 year later showed no evidence of tumor. Prior scintigraphic imaging of therapeutic doses of 131I in 8 of 9 patients demonstrated no distant metastases, further confirming the low-risk status of this group. The staging method predicts that only 0.9% of patients with low-risk papillary carcinoma will have a cause specific death in 20 years. Elevated Tg concentrations have not been shown to forecast independently the survival of patients with low-risk papillary carcinoma. Thus, although frequently encountered, elevated Tg concentrations are unlikely to predict shortened survival in patients with papillary carcinoma for whom low risk has been determined from other data.

Is pregnancy in diabetic women associated with folate deficiency?

OBJECTIVE: To determine whether folate metabolism in pregnant diabetic women is significantly different from that in pregnant nondiabetic women, thus predisposing them to having offspring with major congenital anomalies. RESEARCH DESIGN AND METHODS: A total of 31 pregnant diabetic women and 54 pregnant nondiabetic control subjects were studied at their first prenatal visits. Dietary folate intake, serum folate, red blood cell folate, urinary folate, and homocysteine were measured and compared after controlling for folate supplementation. Among diabetic women the relationships among parameters of folate metabolism and glycemic control were also assessed. RESULTS: There were no significant differences between the pregnant diabetic and non-diabetic women for any measures of folate metabolism after accounting for folate supplementation. In addition, among diabetic women, there were no associations among parameters of folate metabolism and glycemic control. CONCLUSIONS: Abnormal folate metabolism does not appear to occur in pregnant diabetic women. It is unlikely that deranged folate metabolism explains the higher incidence of major anomalies in infants of diabetic mothers. These results do not diminish the importance of periconception folate supplementation or preclude other possible scenarios that could restrict folate use by the embryo, leading to congenital anomalies.

Serum percent-free PSA does not predict extraprostatic spread of prostate cancer.

Percent-free prostate-specific antigen (proportion of free prostate-specific antigen [PSA] to total PSA) has been shown recently in studies on frozen serum samples to be more useful than total PSA alone in distinguishing prostate cancer from benign conditions of the prostate gland. The primary purpose of our study was to determine whether percent-free PSA could predict extraprostatic spread of prostate cancer. We also sought to evaluate the freeze-thaw stability of free PSA. Percent-free PSA values in fresh serum samples were compared with those in aliquots subjected to one to five freeze-thaw cycles. Percent-free PSA values in frozen serum samples from 130 men undergoing radical prostatectomy for clinically localized prostate cancer were compared across pathologic stages. Free PSA levels remained stable for up to five freeze-thaws. Great overlap was found in percent-free PSA values for men with organ-confined disease and those with extraprostatic spread. These results indicate that multiple freeze-thaw cycles do not significantly affect free PSA levels and percent-free PSA is not useful in identifying ideal candidates for radical prostatectomy.

Social economics of childhood glucocorticoid stress response and health.

This study examines socioeconomic conditions, psychosocial stress, and health among 264 infants, children, adolescents, and young adults aged 2 months to 18 years residing in a rural Caribbean village. Fieldwork was conducted over a 9 year period (1988-1996). Research methods and techniques include salivary cortisol radioimmunoassay (N = 22,438), systematic behavioral observations, psychological questionnaires, health evaluations, medical records, informal interviews, and participant observation. Analyses of data indicate complex relations among socioeconomic conditions, stress, and health. Household income, land ownership, parental education, and other socioeconomic measures are weakly associated with child illness. There is no evidence that apparent material benefits of high socioeconomic status--such as improved housing, diet, work loads, and access to private healthcare--have important direct effects on child health in this population. However, social relationships, especially family environment, may have important effects on childhood psychosocial stress and illness. Abnormal glucocorticoid response profiles, diminished immunity, and frequent illness are associated with unstable mating relationships for parents/caretakers and household composition. We suggest that family relationships and concomitant stress and immunosuppression are important intermediary links between socioeconomic conditions and child health.

Social economics of childhood glucocorticoid stress response and health

This study examines socioeconomic conditions, psychosocial stress, and health among 264 infants, children, adolescents, and young adults aged 2 months to 18 years residing in a rural Caribbean village in Dominica. Fieldwork was conducted over a 9 year period (1988-1996). Research methods and techniques include salivary cortisol radioimmunoassay (N = 22, 438), systematic behavioral observation, psychological questionnaires, health evaluation, medical records, informal interviews, and participant observation. Analyses of data indicate complex relations among socioeconomic conditions, stress, and health. Household income, land ownership, parental education, and other socioeconomic measures are weakly associated with child illness. There is no evidence that apparent material benefits of high socioeconomic status such as improved housing, diet, work loads, and access to private health care have important direct effects on child health in this population. However, social relationship, especially family environment, may have important effects on childhood psychosocial stress and illness. Abnormal glucocorticoid response profiles, diminished immunity, and frequent illness are associated with unstable mating relationships for parents/caretakers and household compositon. We suggest that family relationships and concomitant stress and immunosuppression are important intermediary links between socioeconomic conditions and child health.(AU)

Half-life determination of serum free prostate-specific antigen following radical retropubic prostatectomy.

OBJECTIVES: Prostate-specific antigen (PSA) continues to be the the most clinically useful tumor marker for prostate cancer. Recently, several molecular forms of PSA have been detected and characterized. These specific forms, including free PSA and PSA complexed to alpha 1-antichymotrypsin, can be measured and their proportions determined. In doing so, the sensitivity of PSA as a tumor marker can be maintained while the specificity is improved. In order to maximize the clinical utility of free PSA, the half-life and elimination kinetics of free PSA from the serum were determined. METHODS: Twenty-five patients, ages 43-74 years (mean 60 years) with biopsy proven, organ-confined adenocarcinoma of the prostate who underwent anatomic radical retropubic prostatectomy, were identified. For each patient, venous blood samples were obtained preoperatively, and at 60-minute intervals beginning 1 hour after the prostate was removed. The specimens were handled and stored in a consistent fashion. Using the AxSYM immunoassay analyzer (Abbott Diagnostics, Abbott Park, IL), the serum free PSA values were determined and plotted as a function of time for each patient. From the 25 individual elimination curves that were generated, the half-life of serum free PSA was determined. RESULTS: The mean half-life of serum free PSA was 110 minutes +/- 18.6 minutes (SD). Analysis of the individual and cumulative elimination curves indicates that the elimination of free PSA from the serum following radical prostatectomy follows a biphasic pattern. CONCLUSIONS: Unlike PSA, which has a half life of 2-3 days, the half-life of serum free PSA is 110 minutes (1.83 hours). This short half-life may have significant implications for the use of percentage of free PSA as a clinically useful tool in distinguishing patients with early, curable prostate cancer from men with benign prostatic hyperplasia (BPH) only.

Male-female differences in effects of parental absence on glucocorticoid stress response.

This study examines the family environments and hormone profiles of 316 individuals aged 2 months-58 years residing in a rural village on the east coast of Dominica, a former British colony in the West Indies. Fieldwork was conducted over an eight-year period (1988-1995). Research methods and techniques include radioimmunoassay of cortisol and testosterone from saliva samples (N=22,340), residence histories, behavioral observations of family interactions, extensive ethnographic interview and participant observation, psychological questionnaires, and medical examinations.Analyses of data indicate complex, sex-specific effects of family environment on endocrine function. Male endocrine profiles exhibit greater sensitivity to presence of father than do female endocrine profiles. Father-absent males tend to have (a) low cortisol levels during infancy, (b) high or abnormal cortisol profiles during childhood and adolescence, and (c) high cortisol and low testosterone levels during adulthood compared with those of males raised with a resident father. These results indicate that early family environment has significant effects on endocrine response throughout male life histories.

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)

Adrenal axis and hypogonadotropism in the growth-restricted female lamb.

Growth retardation induced by dietary restriction in the lamb results in a decrease in LH pulse frequency and therefore in delayed puberty. Increased circulating cortisol levels have been associated with nutritional restriction in a variety of species. The current study tested the hypothesis that hyperactivity of the adrenal axis sustains hypogonadotropism in the growth-restricted lamb. Our approach was to compare the patterns and levels of circulating cortisol and LH in ovariectomized, growth-restricted (n = 8) and ad libitum-fed (n = 6) lambs. At 37 wk of age, after the growth-restricted lambs had been on the reduced diet for 31 wk, basal cortisol levels were determined hourly for 31 h. In addition, during this period, pulsatile LH and cortisol release was determined during a 4-h period (samples every 12 min). Finally, the cortisol response to a physiologic ACTH stimulus and an audiovisual stimulus (barking dog for 2 min) was determined in frequent samples collected during the last 5 h of the 31-h period. As expected, growth-restricted lambs exhibited a low LH pulse frequency (0.25 +/- 0.10 pulses/h) compared with ad libitum-fed lambs (1.37 +/- 0.07 pulses/h). No diurnal cortisol rhythm was observed in either group, and a similar cortisol pulse frequency occurred in the two groups (1.00 +/- 0.07 pulses/h in growth-restricted lambs and 1.05 +/- 0.10 pulses/h in ad libitum-fed lambs). There was no significant difference between the groups in cortisol pulse amplitude. ACTH administration (i.v.) induced a similar cortisol pulse in 4 of 8 growth-restricted lambs and in 5 of 6 ad libitum-fed lambs.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Differentiation of human pituitary adenomas determines the pattern of chromogranin/secretogranin messenger ribonucleic acid expression.

The distribution of chromogranin/secretogranin (Cg/Sg) mRNAs, determined by Northern and in situ hybridization, was analyzed in 14 cultured pituitary adenomas characterized by immunohistochemistry and hormone secretion in a defined medium in vitro. There were 5 functional GH adenomas, 1 silent GH adenoma, 7 null cell adenomas, and 1 oncocytoma. The null cell adenomas, oncocytoma, and silent GH adenomas were also analyzed by electron microscopy. Most null cell adenomas and the oncocytoma secreted FSH and LH into the culture medium. GH adenomas, which are examples of well differentiated tumors based on morphological examination, expressed significantly more SgIII mRNA compared to the null cell adenomas and oncocytoma (70 +/- 6% vs. 22 +/- 5%; P < 0.001). GH adenomas also expressed significantly less CgA mRNA compared to the less well differentiated null cell adenomas and oncocytoma (27 +/- 6% vs. 67 +/- 4%; P < 0.001), which could be considered less well differentiated based on ultrastructural morphological features. After treatment with phorbol 12-myristate 13-acetate (10(-7) M) for 7 days, there was an increase in the mRNA for CgB and SgII mRNAs in GH and null cell tumors, while dexamethasone treatment for 7 days increased CgA mRNA in GH and null cell adenomas. GnRH treatment for 7 days increased CgB mRNA in null cell adenomas. Phorbol 12-myristate 13-acetate also decreased the percentage of immunoreactive GH cells and GHm RNA, determined by in situ and Northern hybridization analyses. These results indicate that pituitary adenomas have a distinct pattern of Cg/Sg mRNA expression, which appears to be related to the degree of morphological differentiation of these neoplasms, and suggest that the effects of secretagogues on various Cg/Sg mRNA levels may be related to the stimulation of hormone secretion.

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)