Genetic testing of aetiology of intellectual disability in a dedicated physical healthcare outpatient clinic for adults with intellectual disability.

BACKGROUND: No guidelines exist for assessment of aetiology of intellectual disability in adults with intellectual disability by adult physicians, although robust guidelines exist for paediatric populations. It was speculated that the paediatric guidelines would also be suitable for adults. AIMS: In rural/regional setting with limited clinical genetics, to perform a quality assurance evaluation on genetics assessment of aetiology of developmental disability in adults attending a dedicated healthcare clinic for adults with intellectual disability, compared results with paediatric standards, speculates if these seem appropriate for adults and speculates on a role for clinical genetics services. METHODS: Retrospective chart audit of eligible patients looking at genetic clinical assessment, tests selected (molecular karyotype, G banding, metabolics), and yields of positive results. The results were compared with the recommended paediatric guidelines. RESULTS: Of 117 eligible adult patients, ideal genetic history was incomplete for 40% of patients without Down syndrome because of physician cause and lack of information. The number of abnormal genetic results increased from 46% to 66%, mainly from the molecular karyotype, though not all may have been clinically relevant. The improved yield from this test was similar to that in paediatric studies. Use of G banding and metabolic testing could be refined. CONCLUSION: Improvement can be made in clinical genetic assessment, but results generally support use of molecular karyotyping as first tier testing of cause of unknown intellectual disability in adults, as in the case for paediatric populations. The study highlights a necessary complementary role for clinical geneticists to interpret abnormal results.

Factors associated with overweight and central adiposity in urban workers covered by the Workers Food Program of the Brazilian Amazon Region.

OBJECTIVE: To investigate factors associated with overweight and abdominal obesity in male and female workers. METHODS: This is a cross-sectional population-based study. A representative sample of 1,054 workers ranging from 18 to 74 years of age, selected among individuals covered by the Workers´ Food Program living in the Metropolitan region of Belém, Northern Brazil. Health-related behavior and anthropometry were assessed. Fasting blood samples were collected. RESULTS: Overweight prevalence was 38.0% among women and 50.4% among men. Among overweight subjects, there were 6.1% obese women and 10.7% obese men. Multivariate analysis was used to identify social behavior and clinical-biochemical factors associated with increased body adiposity (BMI > 25 kg/m² and increased waist circumference: > 80 cm for women and > 94 cm for men). Variables positively and significantly associated with overweight and abdominal obesity in men according to prevalence ratio (PR) values were: age (1.02), high family income (1.05), smoking (1.36), hypertension (systolic blood pressure, 1.41; diastolic blood pressure, 1.85) and hypertriglyceridemia (2.29). In women, the PR of increased body adiposity was associated with: age (1.02), alcohol intake (1.42), hypertriglyceridemia (1.44), diastolic blood pressure (1.65) and hyperglycemia (1.71). CONCLUSIONS: The association of overweight and abdominal obesity with social behavior variables should be corrected with preventive and educational measures. Furthermore, association of overweight and abdominal obesity with clinical and biochemical variables places the urban workers from the Amazon region assisted by the Workers´ Food Program at a possible risk for morbidity and mortality from increased body adiposity.

Factors associated with overweight and central adiposity in urban workers covered by the Workers Food Program of the Brazilian Amazon Region / Fatores associados ao sobrepeso e adiposidade central em trabalhadores urbanos assistidos pelo Programa de Alimentação do Trabalhador da região amazônica do Brasil

OBJECTIVE: To investigate factors associated with overweight and abdominal obesity in male and female workers. METHODS: This is a cross-sectional population-based study. A representative sample of 1,054 workers ranging from 18 to 74 years of age, selected among individuals covered by the Workers´ Food Program living in the Metropolitan region of Belém, Northern Brazil. Health-related behavior and anthropometry were assessed. Fasting blood samples were collected. RESULTS: Overweight prevalence was 38.0 percent among women and 50.4 percent among men. Among overweight subjects, there were 6.1 percent obese women and 10.7 percent obese men. Multivariate analysis was used to identify social behavior and clinical-biochemical factors associated with increased body adiposity (BMI > 25 kg/m² and increased waist circumference: > 80 cm for women and > 94 cm for men). Variables positively and significantly associated with overweight and abdominal obesity in men according to prevalence ratio (PR) values were: age (1.02), high family income (1.05), smoking (1.36), hypertension (systolic blood pressure, 1.41; diastolic blood pressure, 1.85) and hypertriglyceridemia (2.29). In women, the PR of increased body adiposity was associated with: age (1.02), alcohol intake (1.42), hypertriglyceridemia (1.44), diastolic blood pressure (1.65) and hyperglycemia (1.71). CONCLUSIONS: The association of overweight and abdominal obesity with social behavior variables should be corrected with preventive and educational measures. Furthermore, association of overweight and abdominal obesity with clinical and biochemical variables places the urban workers from the Amazon region assisted by the Workers´ Food Program at a possible risk for morbidity and mortality from increased body adiposity.

OBJETIVO: Investigar os fatores associados ao sobrepeso e a obesidade abdominal em trabalhadores de ambos os sexos. MÉTODO: Estudo transversal de base populacional, de uma amostra representativa de 1054 trabalhadores, com idade entre 18 e 74 anos, assistidos pelo Programa de Alimentação do Trabalhador na região metropolitana de Belém do Pará, na região norte do Brasil. Parâmetros relacionados à saúde e medidas antropométricas foram obtidas e amostra de sangue foram coletadas. RESULTADOS: A prevalência de sobrepeso foi de 38 por cento nas mulheres e 50,4 por cento nos homens. Dentre os indivíduos com sobrepeso, 6,1 por cento das mulheres eram obesas e 10,7 por cento dos homens tinham obesidade. Análise multivariada foi utilizada para identificar os fatores sociocomportamentais e clínico-bioquímicos associados com o aumento da adiposidade corporal (IMC > 25kg/m2 e circunferência de cintura > 80cm para mulheres e >94cm para homens). As variáveis e a razão de prevalência (PR) associadas ao sobrepeso e adiposidade abdominal nos homens foram: idade (1,02), renda familiar alta (1,05), fumo (1,36), hipertensão (pressão arterial sistólica 1,41 e pressão arterial diastólica 1,85) e hipertrigliceridemia (2,29). Nas mulheres as razões de chance para sobrepeso e adiposidade abdominal foram: idade (1,02), consumo de álcool (1,42), hipertrigliceridemia (1,44), pressão arterial diastólilca (1,65) e hiperglicemia (1,71). CONCLUSÃO: A associação do sobrepeso e obesidade abdominal com parâmetros sociocomportamentais devem ser corrigidos com medidas educativas e preventivas. Além disso, a associação de sobrepeso e obesidade abdominal com parâmetros clínicos e bioquímicos coloca os trabalhadores de Belém do Pará, assistidos pelo Programa de Alimentação do Trabalhador, em possível risco de morbidades e mortalidade precoce pelo aumento de adiposidade corporal.

First isolation of Cryptococcus gattii molecular type VGII and Cryptococcus neoformans molecular type VNI from environmental sources in the city of Belém, Pará, Brazil.

Cryptococcus neoformans and Cryptococcus gattii are important agents of meningoencephalitis in humans in the city of Belém. This clinical data suggests that the region may be a highly endemic area for the pathogenic Cryptococcus species within the state of Pará (PA), Northern Brazil. Preliminary analysis of 11 environmental samples from the city of Belém showed two positive locations, including a hollow of a kassod tree (Senna siamea) colonized simultaneously by C. gattii molecular type VGII and C. neoformans molecular type VNI, and a birdcage in a commercial aviary positive for C. neoformans, molecular type VNI. This is the first evidence of an environmental occurrence of molecular types VNI and VGII in PA.

First isolation of Cryptococcus gattii molecular type VGII and Cryptococcus neoformans molecular type VNI from environmental sources in the city of Belém, Pará, Brazil

Cryptococcus neoformans and Cryptococcus gattii are important agents of meningoencephalitis in humans in the city of Belém. This clinical data suggests that the region may be a highly endemic area for the pathogenic Cryptococcus species within the state of Pará (PA), Northern Brazil. Preliminary analysis of 11 environmental samples from the city of Belém showed two positive locations, including a hollow of a kassod tree (Senna siamea) colonized simultaneously by C. gattii molecular type VGII and C. neoformans molecular type VNI, and a birdcage in a commercial aviary positive for C. neoformans, molecular type VNI. This is the first evidence of an environmental occurrence of molecular types VNI and VGII in PA.

Consensus guidelines into the management of epilepsy in adults with an intellectual disability.

BACKGROUND: Epilepsy has a pervasive impact on the lives of people with intellectual disability and their carers. The delivery of high-quality care is impacted on by the complexity and diversity of epilepsy in this population. This article presents the results of a consensus clinical guideline process. RESULTS: A Delphi process identified a list of priority areas for the development of evidence-based guidelines. All guidelines were graded and consensus on scoring was achieved across the guideline group. CONCLUSION: There is a dearth of high-quality evidence from well-constructed studies on which to base guidance. However, the development of internationally derived consensus guidelines may further support the management of epilepsy in adults with an intellectual disability.

Effects of Helicobacter pylori eradication among adults with intellectual disability.

BACKGROUND: Compared to the general population, Helicobacter pylori infection is more common among adults with intellectual disability (ID) and is associated with greater levels of disability, maladaptive behaviour, and institutionalization. Little information exists about the effects of eradication therapy in this group, so we aimed to evaluate: (1) success of a standard H. pylori eradication protocol; (2) frequency of side-effects; and (3) impact of eradication on level of functional ability and maladaptive behaviour. METHOD: A cohort of adults with ID underwent assessment of their levels of function and maladaptive behaviour, medical history, physical examination, and H. pylori testing using serology and faecal antigen tests. Some received standard H. pylori eradication therapy. Twelve months later, participants underwent repeat assessment, were grouped by change in H. pylori status and compared. RESULTS: Of 168 participants, 117 (70%) were currently infected with H. pylori at baseline, and 96 (82%) of the 117 were given standard H. pylori eradication therapy. The overall eradication rate was 61% but 31% reported side-effects. Institutional status of the participants, their level of behaviour or function, and number of comorbid medical conditions were not associated with failure of eradication. There were no statistically significant differences in level of behaviour or function, ferritin, or weight between the groups in whom H. pylori was eradicated or stayed positive. CONCLUSION: Adults with ID have lower H. pylori eradication and higher side-effect rates than the general population. Levels of maladaptive behaviour and disability did not improve with eradication and thus greater levels of maladaptive behaviour or disability appear to be risk factors for, rather than consequences of, H. pylori infection.

Synchronization of estrus in postpartum beef cows and virgin heifers using combinations of melengestrol acetate, GnRH, and PGF2alpha.

The efficacy of various combinations of melengestrol acetate (MGA), GnRH, and PGF2alpha for the synchronization of estrus in Angus-based beef cattle was compared. Hormones were administered as follows: MGA, 0.5 mg x animal(-1) x d(-1) mixed in a grain carrier; GnRH, 100 microg i.m.; PGF2alpha, 25 mg i.m. In Exp. 1, 2, and 3, cows were randomly assigned to treatments by parity and interval postpartum. The detection of estrus and AI were conducted from d -2 until 72 to 96 h after PGF2alpha, at which time cows not detected to be in estrus received GnRH and fixed-time AI (TAI). Data were analyzed separately for primiparous and multiparous cows. In Exp. 1, cows (n = 799) at three locations received GnRH on d -7 and PGF2alpha on d 0 and either no further treatment (GnRH-PGF) or short-term MGA from d -6 through d -1 (STMGA). Among multiparous cows, conception rate at TAI was greater (P < 0.05) for STMGA (41%, 47/115) than for GnRH-PGF treated cows (26%, 24/92). Across herds and parity, synchronized AI pregnancy rate (SPR) was not affected (P > 0.10) by treatment (GnRH-PGF vs. STMGA; 54%, 210/389 vs. 57%, 228/402). In Exp. 2, cows (n = 484) at three locations received either STMGA or long-term MGA from d -32 through d -19, GnRH on d -7, and PGF2alpha on d 0 (LTMGA). Among primiparous cows, SPR was greater (P < 0.01) in LTMGA (65%, 55/85) than STMGA-treated cows (46%, 40/87). Treatment had no effect (P > 0.10) on SPR among multiparous cows (STMGA vs. LTMGA; 59%, 92/155 vs. 64%, 101/157). In Exp. 3, cows (n = 838) at four locations received the LTMGA treatment and either no further treatment or an additional period of MGA exposure from d -6 through d -1 (L&STMGA). Among primiparous cows, SPR tended to be influenced (P < 0.10) by the herd x treatment interaction and was greater (P < 0.01) among L&STMGA (86%, 19/22) than LTMGA-treated cows (56%, 14/25) at a single location. Among multiparous cows, SPR was lower (P < 0.05) in L&STMGA (46%, 165/358) than LTMGA-treated cows (55%, 184/336). In Exp. 4, Angus heifers (n = 155) received either STMGA or 14 d of MGA (d -32 through d -19) and PGF2alpha on d 0 (MGA-PGF). The detection of estrus and AI were conducted from d -2 to d 6. Interval to estrus was greater (P < 0.05) and estrous response was lower (P < 0.05) in STMGA than MGA-PGF-treated heifers. In conclusion, primiparous cows responded more favorably to longer-duration MGA treatments than did multiparous cows. All protocols achieved sufficient SPR to justify their use for improved reproductive management of postpartum beef cows.

Recurrence of Helicobacter pylori infection in adults with intellectual disability.

Although Helicobacter pylori infection is very common among particular groups of adults with intellectual disability, the rate of recurrence (reinfection or recrudescence) is unknown in this population. Thirty-six months after successful treatment of H. pylori, 28 adults with intellectual disability were retested using the faecal antigen test. Six (21%) of 28 patients tested positive, giving an approximate yearly recurrence rate of 7%, a rate considerably higher than that in the general population (<1%). It is recommended that adults with intellectual disability who have had successful treatment of H. pylori be retested for an interval of 3-5 years after treatment.

Synchronization of estrus in virgin beef heifers using melengestrol acetate and PGF2alpha: an efficacy comparison of cloprostenol and dinoprost tromethamine.

This study compared the efficacy of two sources of PGF2alpha on the reproductive performance of virgin beef heifers, after synchronization of estrus using melengestrol acetate (MGA) and PGF2alpha. Angus-based heifers (n = 1002) in five herds were fed 0.5 mg per head per day of MGA for 14 days. Nineteen days after the last day of MGA feeding, heifers were randomly assigned to receive (i.m.) either 0.5 mg cloprostenol (n = 504; Estrumate, E) or 25 mg dinoprost tromethamine (n = 498; Lutalyse, L) as a source of exogenous PGF2alpha. Heifers were observed twice daily for 5 days for signs of estrus and artificially inseminated 8-12 h later, except in herd A, wherein animals not detected in estrus by 80 h after PGF2alpha were mass-mated and no longer monitored for signs of estrus. Estrumate and Lutalyse were equally (P > 0.1) effective among all response variables evaluated, including estrus response (E, 89% and L, 86%), conception rate (E, 67% and L, 67%), and synchronized pregnancy rate (E, 61% and L, 57%). Synchrony of estrus was not affected (P > 0.1) by PGF2alpha source, and peak estrus response occurred 60 h post-PGF for both treatments. Conception rate to timed insemination was not different (P > 0.1) among Estrumate- and Lutalyse-treated heifers within herd A (14%, 4/28 and 7%, 2/29, respectively). Herd had a significant (P < 0.05) effect on all indicators of reproductive performance. Conception rates within herds A and D were influenced by technician (P < 0.05), however, this effect was balanced across treatments and no treatment by technician interaction was detected. In conclusion, when administered 19 days after a 14-day MGA feeding period, cloprostenol and dinoprost tromethamine are equally efficacious for synchronous induction of a fertile estrus in virgin beef heifers.

Environmental, medical, behavioural and disability factors associated with Helicobacter pylori infection in adults with intellectual disability.

In institutionalized adults with intellectual disability (ID), Helicobacter pylori infection occurs at approximately twice the rate it appears in the general population, and it may be responsible for the twofold higher rates of peptic ulcer disease and gastric cancer in this population. Medical, behavioural and additional environmental factors, as well as level of ID, may be related to the risk of infection with H. pylori. One hundred and sixty-eight adults with ID who were currently, had previously been or had never been institutionalized underwent a biopsychosocial evaluation. This included assessment of: level of ID using the Adaptive Behaviour Scale (ABS) Part I; levels of maladaptive behaviour using the ABS Part II; demographic, medical and environmental factors; as well as H. pylori tests using serology and faecal antigen. The overall rates of past or current infection with H. pylori in institutionalized and previously institutionalized participants were about twice that of the overall group of never-institutionalized participants, i.e. 87% and 79% compared to 44%, respectively (P < 0.001). The rates of H. pylori infection appeared to increase with age in the never-institutionalized group, but were consistently high across all ages in the other groups. The rate of infection was higher in those institutionalized for more than 5 years (95% versus 76%, P=0.02), in those with flatmates with excessive oral secretions (65% versus 21%, P < 0.001) or faecal incontinence (67% versus 27%, P < 0.001), and in those with more chronic illness and medications. All mean domain scores of the ABS Part I (Intellectual Disability) were significantly lower (indicating more severe ID) in the group currently infected with H. pylori compared to their non-infected counterparts. The majority of mean domain scores of the ABS Part II (Behaviour) were also worse, with half of these score differences reaching statistical significance in the currently infected group. The presence of alarm symptoms (e.g. vomiting, weight loss, haematemesis and melena), iron deficiency and body mass index were not significantly different in currently infected subjects. Adults with ID appear to be particularly at risk of infection with H. pylori. Environmental associations with infection include past or current institutionalization, a longer period of institutionalization, living with flatmates with excessive oral secretions and faecal incontinence. Medical associations include chronic disease and more medications, but not alarm symptoms or body mass index. Demographic associations may include increasing age in never-institutionalized adults, but no age effect in currently or previously institutionalized individuals. Psychosocial associations include more severe ID and maladaptive behaviour with current infection.

Flavonóides de Cissus verticillata e a atividade hipoglicemiante do chá de suas folhas

Cissus verticillata, a Vitaceae very used in the traditional medicine in Pará and Minas Gerais State - Brazil, was investigated in order to validate its indication for the hyperglycaemia control. The aqueous extract reduces the normal glycaemia of male white Wistar rats in about 19.5 percent. The hypoglycaemic effect of this extract could be related to the flavonoids found in the preparation. Luteolin, Kaempferol and Luteolin-3'-sulphate could be isolated from the aqueous extract after acid hydrolysis.

Emotional distress induced rhabdomyolysis in an individual with carnitine palmitoly-transferase deficiency.

A 48-year-old male patient with underlying CPT II enzyme deficiency is described. Emotional stress appeared to precipitate recurrent myalgias, rhabdomyolysis and reversible renal impairment over a 40-year period. Our search of the English literature indicates this to be the first time that the emotional stress has been documented to precipitate the CPT II syndrome. Although the pathogenesis of this syndrome has yet to be established, existing knowledge is briefly reviewed and the likely metabolic and neuroendocrine mechanisms which link emotional stress to muscle metabolism are examined. These mechanisms influence the extent of lipolysis or glycolysis that occurs during the process of muscle ATP generation. It is suggested that neuroendocrine and other stress related changes which favour lipolysis over glycolysis adversely affect muscle energy metabolism in patients whose mitochondria are deficient in CPT II enzyme. Possible treatment strategies are those that favour glycolysis over fatty acid metabolism and include a variety of ways of modulating sympathetic and parasympathetic tone. The use of carbohydrate supplementation beta-blockers and anxiolytic agents is discussed.

Preparation and use of specific antibodies to the beta-I and beta-II subunits of gonadotropic hormone from Fundulus heteroclitus pituitary.

Fundulus heteroclitus naturally spawns with a semilunar periodicity throughout most of the year in its southernmost habitat, an activity that can be maintained in the laboratory. The alpha and two beta subunits comprising F. heteroclitus gonadotropic hormones (GtHs) I and II have been sequenced, and antibodies have been raised against unique peptides found in each of the two beta subunits. On immunoblots of pituitary proteins, each antibody recognizes a single band with a molecular mass of 16-17 kDa, somewhat larger than the deduced sizes (11-13 kDa) of the unglycosylated subunits. Each antibody also recognizes a different subset of pituitary cells in the central (GtH I) and peripheral (GtH II) proximal pars distalis, regions that display the typical tinctorial properties of gonadotrops. The distribution and distinct separation of cells containing GtH beta subunits I and II thus differ from those found for previously described teleost species, most of which are salmonids that engage in a single spawning episode during the year. The availability of these antibodies thus makes F. heteroclitus an inexpensive, easily manipulated model system for studies on the hormonal regulation of fractional spawning common to a large class of commercially important species other than salmonids.

Bafilomycin A1 inhibits proteolytic cleavage and hydration but not yolk crystal disassembly or meiosis during maturation of sea bass oocytes.

Oocytes of the black sea bass, Centropristes striata, were enlarged in volume more than three-fold over a 24-hr period during oocyte maturation, both in vivo and in vitro. At the same time, the opaque oocytes clarified while the crystalline yolk inclusions lost their ordered structure, fused with one another, and formed a continuous electron-lucent mass. The oocyte size increase was due almost entirely to water uptake, which was accompanied by the accumulation of Na+, K+, and free amino acids (FAAs). The absolute amounts of each of these small molecular weight osmotic effectors increased 2x, 4x, and over 10x, respectively, indicating that the generation of FAAs is the major cause of water uptake during maturation. Amino acid analyses indicated that the amounts of all amino acids except taurine increased, so that selective amino acids were not produced during maturation. The increase in FAAs was accompanied by the loss of certain high-molecular-weight yolk proteins and the generation of many smaller peptides. Oocytes stimulated to undergo maturation in the presence of bafilomycin A1, a specific inhibitor of the vacuolar ATPase-dependent proton pump, clarified and underwent maturation but did not increase significantly in size. Cytological examination revealed that yolk crystals fused and became homogeneous but maintained their electron density. No evidence of proteolysis was found in bafilomycin A1-treated oocytes and the generation of FAAs together with hydration was inhibited in a dose-dependent manner (I50 = 3 nM bafilomycin A1). Taken together, we postulate that the pronounced oocyte hydration in marine teleosts that spawn pelagic (floating) eggs is accomplished by a two-step process whereby (i) K+ influx promotes yolk crystal disassembly and yolk sphere fusion and (ii) acidification of the yolk spheres activates yolk proteolysis and concomitant hydration. Bafilomycin A1 inhibits only the second step so that many of the events of oocyte maturation, including germinal vesicle breakdown, occur in its presence but oocyte hydration is suppressed.

Effect of GnRH pretreatment on reproductive performance of postpartum suckled beef cows following synchronization of estrus using GnRH and PGF2alpha.

The effect of GnRH pretreatment on estrus detection rate, precision of estrus, and reproductive performance of postpartum beef cows synchronized to estrus using GnRH and PGF2alpha was evaluated. In Exp. 1, Angus cows (n = 87) were randomly assigned by parity, postpartum interval, and body condition score (BCS) to receive either 1) GnRH on d -7 and PGF2alpha on d 0 (GP) or 2) the GP treatment and an additional injection of GnRH on d -16 (GGP). Estrus detection and AI were conducted twice daily from d -3 to d 3. At 72 h after PGF2alpha, all animals not previously detected in estrus were bred by AI and received a concurrent injection of GnRH (TAI). Synchronized pregnancy rates were numerically increased (P = 0.15) in cows treated with GGP (55%) compared with those on the GP treatment (44%). In Exp. 2, 1,276 spring-calving, suckled beef cows in nine herds were randomized to treatments as described for Exp. 1, except that the initial GnRH injection for the GGP treatment was administered on d -14. Herd affected all indicators of reproductive performance (P < 0.05). The percentage of animals detected in estrus prematurely (d -3 to d 0; 7%) was not affected by treatment. Estrus response rate was influenced by postpartum interval (< 60 vs > or = 60; 61 vs 73%; P < 0.01) and a three-way interaction of parity, BCS, and treatment (P < 0.01). Within animals with a BCS > or = 5.5, the GGP treatment tended to increase the detection of estrus in primiparous cows (GP vs GGP; 76 vs 91%; P = 0.11) and decrease detection in multiparous cows (GP vs GGP; 78 vs 72%; P < 0.10). However, because conception rate to TAI in animals with a BCS > or = 5.5 was greater (P < 0.05) in the GGP than in the GP group (28 vs 8%, respectively), this interaction was interpreted to represent a shift in interval to estrus induced by the GGP treatment, rather than a reduction in the synchronization of ovarian function. Conception rates of animals inseminated to an observed estrus did not differ among treatments (P = 0.15). Synchronized pregnancy rate tended (P = 0.06) to be greater in GGP- (53%) than in GP-treated animals (47%). In conclusion, pretreatment with GnRH tended to increase pregnancy rates during a 6-d synchronization period, primarily through enhanced conception rates of cows bred by TAI. In contrast to our hypothesis, GnRH pretreatment did not increase the percentage of animals detected in estrus or the precision of estrus expression.

Synthesis and preliminary evaluation of MP-2269: a novel, nonaromatic small-molecule blood-pool MR contrast agent.

A nonaromatic, small-molecule, gadolinium(3+)-chelate code named MP-2269 was synthesized and evaluated in animals as a potential MR contrast agent for blood pool. The ligand of MP-2269 was prepared by conjugating a lipophilic, albumin-binding moiety, 4-pentylbicyclo[2.2.2]octane-1-carboxylic acid, to an amino-functionalized DTPA derivative by means of a diaspartic acid linker. Proton relaxometry studies in vitro yielded spin-lattice relaxivities (R1) for MP-2269 of 6.2, 20.0 and 26.1 mM(-1)sec(-1) in water, rabbit blood, and human blood, respectively. The enhanced relaxivities in blood indicate significant binding of the agent to blood proteins. At a dose of 45 micromol/kg, MP-2269 showed a biphasic rabbit blood clearance profile with half-lives of 4.7 and 142 minutes, respectively, for the fast and slow components. In rats, the agent is cleared predominantly through the hepatobiliary pathway (approximately 70% in 24 h by this mode). The LD50 value of MP-2269 is approximately 3.0 mmol/kg in mice. Preliminary MR angiograms obtained in the rabbit showed excellent enhancement of blood vessels. Hence, MP-2269 has potential for future exploitation as a contrast agent for MR angiography.