Interaction of cyanoketone and other steroid nitriles with cytochrome oxidase, hemoglobin, and cytochrome P-450.

The inhibitory activity of cyanoketone (CNK; 2alpha-cyano-4,4,17alpha-trimethyl-17beta-hydroxy-5-androsten-3-one), was investigated for enzymes of the respiratory chain and cholesterol side chain cleavage (CSCC). In bovine corpus luteum mitochondria incubated with [26-14C]cholesterol, 500 micron CNK caused 90% inhibition of pregnenolone synthesis. Comparable results were obtained with adrenal and placental mitochondria. Addition of CNK to bovine corpus luteum mitochondria or to cytochrome P-450 purified from this source elicited a concentration-dependent, reverse type I difference spectrum with an absorption maximum at about 423 nm and a minimum at about 395 nm, confirming binding to oxidized cytochrome P-450. This spectral change resembles those of steroids which inhibit CSCC. In mitochondrial preparations, CNK induced a second peak at about 445 nm. This peak was similar to that elicited by the interaction of potassium cyanide with cytochrome a3 when the former is added to rabbit heart mitochondria which are devoid of P-450. Like cyanide, CNK block mitochondrial respiration at the cytochrome oxidase site, and induced spectral changes in human hemoglobin. Therefore, this peak at 445 nm probably represents the interaction of CNK with oxidized cytochrome a3. Several other steroid nitriles had little, if any, effect on CSCC activity, nor did they induce spectral changes with cytochrome oxidase or hemoglobin. It appears that the steroid configuration of CNK is responsible for the binding to P-450 and inhibition of CSCC, whereas the binding to cytochrome a3 and hemoglobin and the inhibitory effect on electron transfer are probably related to the cyano group of CNK.

Treatment of women with the galactorrhea-amenorrhea syndrome with pyridoxine (vitamin B6).

Three women with the galactorrhea-amenorrhea syndrome and elevated prolactin concentrations experienced a return of regular ovulatory menses within 37-94 days after starting pyridoxine treatment (200-600 mg/day). In each the galactorrhea ceased and serum prolactin levels were maintained in the normal range while taking pyridoxine. In two other women with prolonged secondary amenorrhea but without hyperprolactinemia or galactorrhea, pyridoxine at dosages up to 600 mg/day did not restore ovulatory menses. Pyridoxine treatment was also ineffective in decreasing profuse galactorrhea in one woman with normal prolactin levels and regular ovulatory menses. In the three women effectively treated with pyridoxine, the galactorrhea returned, serum prolactin levels increased, and the menses ceased after discontinuing pyridoxine. These results imply that pyridoxine, by decreasing the excessive secretion of prolactin, may be useful in the long-term medical management of women with hyperprolactinemia and the galactorrhea-amenorrhea syndrome.

Food and nutrition skills of mentally retarded adults: assessment and needs.

Nutrition assessment showed that 48% of the mentally retarded adults in this study were obese, pointing to present and/or past energy imbalances (11,14). Approximately 43% of the clients were consuming less than 50% of the RDAs for one or more nutrients. Diets were most frequently low (less than 75% RDAs) in iron, vitamin A, and calcium. Other problems included difficulties in shopping, menu planning, and food preparation. Clients scored a mean of 53.2% on the nutrition knowledge test. This program has made great progress in developing its clients' food and nutrition skills. But the study showed that ongoing reinforcement of basic nutrition knowledge and skills is critically needed, along with a practical cookbook to aid clients in applying nutrition principles to daily menu planning and food preparation. To fill the latter need, a food and nutrition manual for self-sufficient adults is currently being developed.

Implication of ligand modified spectra of cytochrome P-450 associated with pregnenolone synthesis in mitochondria from corpus luteum.

The implications of ligand modified spectra of cytochrome P-450 in mitochondria from corpus luteum are considered. Mitochondria from bovine corpus luteum contain a single cytochrome P-450 which oxidizes cholesterol to pregnenolone and isocaproaldehyde. These mitochondria and the cytochrome P-450 purified from these mitochondria yield Type I spectral changes with substrates, reverse Type I spectral changes with certain steroid substrates, steroid products and unrelated steroid ligands. Nitrogenous ligands yield Type II spectral changes. Mitochondrial and purified cytochrome P-450 preparations are equivalent in this study. The inhibitory effects on the cholesterol monooxygenase are directly related to the spectral changes induced by Type II ligands. Lastly, it is suggested that a similar relationship exists with reverse Type I ligands.

Recent changes in the sociodemographic profile of sterilization acceptors in Nepal.

The records of 8056 Nepalese males and 9291 females sterilized from 1979-1983 were analyzed. Compared with data from previous studies (1970-1976), significant decreases occurred in the average age of female acceptors (30.6 vs. 33.1, P less than 0.01) and wives of male acceptors (28.4 vs. 31.7, P less than 0.01). Also, the average number of living children per couple decreased by one child (4.9-3.9, P less than 0.01) for male acceptors and 0.6 (4.8-4.2, P less than 0.01) for female acceptors. Finally in 83.2% of the cases, the operation was performed within 3 years of the last delivery.

PIP: The records of 8056 Nepalese males and 9291 females sterilized from 1979-1983 were analyzed. Compared with data from previous studies (1970-1976), significant decreases occurred in the average age of female acceptors (30.6 vs. 31.7, P0.01) and wives of male acceptors (28.4 vs. 31.7, P0.01). Also, the average number of living children per couple decreased by 1 child (4.9-3.9, P0.01) for male acceptors and 0.6 (4.8--4.2, P0.01) for female acceptors. Finally in 83.2% of the cases, the operation was performed within 3 years of the last delivery. Since 1970-1971 there has been a progressive rise in the % of sterilization acceptors referred by the health worker. For male acceptors there has been nearly a 3-fold increase. The vast majority of both male and female acceptors elected to have their operations within 2 years of the last delivery, regardless of the outcome. It appears that most couples time sterilization to coincide with the cessation of breastfeeding. Care must be taken to guard against the health worker being overly zealous in motivating and mobilizing potential voluntary sterilization contraception candidates.

Nutritional assessment of the hospitalized patient.

Nutritional assessment is essential for optimal care of the hospitalized patient. Clinical observation, certain anthropometric measurements, diet history and determination of serum albumin, total lymphocyte count and nitrogen balance are recommended. Serum albumin and the lymphocyte count are considered 'key" parameters which permit an instant assessment in emergency situations. An initial assessment should always be made on the basis of whatever pertinent information is available.

Barriers to effective family planning in Nepal.

To investigate why family planning (FP) services in the Kathmandu Valley of Nepal are underused, a study was initiated under the auspices of the Nepal Family Planning/Maternal--Child Health Project. The study was intended to provide a user perspective, by examining interactions between FP clinic staff and their clientele. "Simulated" clients were sent to 16 FP clinics in Kathmandu to request information and advice. The study revealed that in the impersonal setting of a family planning clinic, clients and staff fall into traditional, hierarchical modes of interaction. In the process, the client's "modern" goal of limiting her family size is subverted by the service system that was created to support this goal. Particularly when status differences are greatest, that is, with lower-class and low caste clients, transmission of information is inhibited.

PIP: To investigate why family planning (FP) services in the Kathmandu Valley of Nepal are underused, a study was initiated under the auspices of the Nepal Family Planning/Maternal Child Health Project. The question behind the study was whether the professional providers of family planning services are themselves inhibiting effective use of contraception. The purpose of the study was to examine interactions between family planning clinic staff and their clientele. For this purpose, 6 couples and 2 individual women with different socioeconomic backgrounds posed as clients (simulated clients) and were sent to 16 of the 25 family planning clinics in the Kathmandu Valley over a period of about a month. The simulated clients were trained individually and as couples, using role-playing techniques and acting out roles that did not deviate much from their actual life situations. 3 groups of simulated clients with different taste, class and educational backgrounds were trained and sent to nearby family planning clinics. Group A consisted of 2 high caste, urban couples. Group B consisted of 2 lower middle-class couples and 2 individual women. The 2 couples in Group C were lower-class. The accounts provided by the simulated clients were analyzed qualitatively for overall content, and rated using a scale of 1 through 3, based on the accuracy of the family planning information provided, attitude of the staff toward the client and bias of the staff toward the client. The underlying assumption was that a good attitude and lack of bias on the part of family planning staff would be conducive to a desirable outcome, that is, a well-informed, free decision by the client to adopt a particular family planning method. Directly and indirectly, the study revealed a number of barriers to provision and effective use of family planning services in the urban areas of Nepal. The scores indicate that the family planning information provided at most clinics is inadequate or incorrect in many cases. The manner in which the information is presented is apt to drive clients away. In the impersonal setting of a family planning clinic, clients and staff fall into traditional, hierarchical modes of interaction. Moreover, the quality of the services was positively related to the socioeconomic status of the client. Unsophisticated lower-class clients are likely to receive scantier, less accurate information and less courteous treatment than educated middle-class clients. The former's negative perceptions of family planning and family planning clinics probably become disseminated among friends and neighbors. A neighborhood-based program would be more effective than the clinic-based system as it now functions. An alternative or complementary program might focus on upgrading the communication skills of family planning staff within clinics.

A focused approach to quality of care assessment in family planning.

An approach to quality of care assessment for family planning based on management-by-objectives has been tested in 18 clinics. Key indicator standards were developed by the family planning agencies themselves and objective survey instruments designed to measure performance against the standards. Results were made available quickly to each clinic and led to operational changes in the majority, with evidence of improved performance and willingness to use evaluation of care as a means for clinic management. Analyses of the aggregated data showed wide variations in performance over several indices of care.