Chronic treatment of female rhesus monkeys with low doses of the antiprogestin ZK 137 316: establishment of a regimen that permits normal menstrual cyclicity

Large doses of antiprogestin typically disrupt menstrual cyclicity. A chronic low-dose regimen of the potent new antiprogestin ZK 137 316, which permits continued menstrual cyclicity but alters gonadal- reproductive tract activity, was established. Rhesus monkeys received vehicle (n = 6) or 0.01 (n = 8), 0.03 (n = 8) or 0.1 (n = 5) mg ZK 137 316/kg body weight daily for five menstrual cycles (C-1 to C-5). Oestradiol, progesterone and gonadotrophin profiles were normal during cycles involving vehicle and 0.01 and 0.03 mg ZK 137 316/kg body weight. In the 0.1 mg/kg group, mid-cycle oestradiol and gonadotrophin surges, and subsequent progesterone production, were absent in C-3 and C-5. Ovarian cyclicity was accompanied by timely menstruation in the vehicle and 0.01 mg/kg groups. By C-3, half the animals in the 0.03 mg/kg group and all animals in the 0.1 mg/kg group were amenorrhoeic. A corpus luteum was noted during the mid-luteal phase of C-5 in the vehicle, 0.01 mg/kg and 0.03 mg/kg groups. Large antral and cystic follicles were evident in the 0.1 mg/kg group. Thus, a daily treatment with 0.01 mg/kg ZK 136317 permitted normal menstrual cyclicity in macaques. While the daily administration of 0.03 mg/kg ZK 136 317 allowed ovarian cyclicity, menstruation was disrupted in some animals. Increasing the dose to 0.1 mg/kg antagonized pituitary function and resulted in anovulation and amenorrhoea. A chronic low-dose regimen of the antiprogestin ZK 137 316, which permits normal ovarian/menstrual cyclicity, has potential as a contraceptive in women.      

Interchromosomal duplications of the adrenoleukodystrophy locus: a phenomenon of pericentromeric plasticity

A 9.7 kb segment encompassing exons 7-10 of the adrenoleukodystrophy (ALD) locus of the X chromosome has duplicated to specific locations near the pericentromeric regions of human chromosomes 2p11,10p11, 16p11 and 22q11. Comparative sequence analysis reveals 92-96% nucleotide identity, indicating that the autosomal ALD paralogs arose relatively recently during the course of higher primate evolution (5-10 million years ago). Analysis of sequences flanking the duplication region identifies the presence of an unusual GCTTTTTGC repeat which may be a sequence-specific integration site for the process of pericentromeric- directed transposition. The breakpoint sequence and phylogenetic analysis predict a two-step transposition model, in which a duplication from Xq28 to pericentromeric 2p11 occurred once, followed by a rapid distribution of a larger duplicon cassette among the pericentromeric regions. In addition to facilitating more effective mutation detection among ALD patients, these findings provide further insight into the molecular basis underlying a pericentromeric-directed mechanism for non- homologous interchromosomal exchange.      

Correlation Between Regional Specificity of Antisperm Antibodies to the Spermatozoan Surface and Complement-Mediated Sperm Immobilization

ABSTRACT: Sera from men at risk for immunity to spermatozoa were screened for antisperm antibodies by immunobead binding following passive antibody transfer to antibody-free sperm of fertile donors. The percent motile sperm after incubation in diluted antibody positive serum in the presence of complement was compared with the regional distribution of immunoglobulins bound to the sperm surface. The extent of complement-mediated sperm immobilization varied with immunoglobulin class and with the location of antibody bound to the sperm surface. Tests utilizing complement-mediated immobilization of sperm are insensitive to the presence of antibodies of IgG and IgA classes that are directed against the head, the distal one-fifth of the sperm tail principal piece, or the tail end piece. A high degree of immobilization was found only when IgG binding occurred on the distal two-fifths to three-fifths of the principal piece of the tail or when IgM bound to the sperm tail end piece.     

The salivary microbiota as a diagnostic indicator of oral cancer: A descriptive,non-randomized study of cancer-free and oral squamous cell carcinoma subjects

Background  

The purpose of the present investigation was to determine if the salivary counts of 40 common oral bacteria in subjects with an oral squamous cell carcinoma (OSCC) lesion would differ from those found in cancer-free (OSCC-free) controls.     

ROLE OF DOPAMINE AND α-ADRENORECEPTORS IN THE CONTROL OF GASTRIC EMPTYING IN THE RAT: POSSIBLE INVOLVEMENT IN THE MECHANISM OF ACTION OF METOCLOPRAMIDE

• 1 The object of the study was to investigate the effects of dopamine receptor and a-adrenoreceptor agonists and antagonists on the gastric emptying of a liquid test meal in conscious rats and the possible involvement of these receptors in the mechanism of action of metoclopramide.
• 2 The gastric emptying of a liquid test meal in conscious chronic gastric fistula rats was delayed following subcutaneous administration of either 6,7-ADTN (1-50 mgikg) or clonidine (0.05-1 mgikg). Phenylephrine (0.2–10 mg/kg s.c.) had no effect on gastric emptying, suggesting that dopamine and a2-, but not al-adrenoreceptors may be involved in the control of gastric emptying in the rat.
• 3 Phentolamine (0.2–5 mg/kg s.c.) and prazosin (0.1–0.5 mg/kg s.c.) potentiated the delay in gastric emptying induced by 6,7-ADTNY whilst yohimbine (1–5 mg/kg s.c.) and prazosin (0.1–0.5 mg/kg s.c.) reversed the delay in emptying induced by clonidine. All three a-adrenoreceptor antagonists also delayed gastric emptying in the absence of agonist. Propranolol(0.2–5 mgikg s.c.) had no effect on either normal or delayed gastric emptying.
• 4 Both metoclopramide (1–10 mg/kg s.c.) and haloperidol (0.02–0.5 mgikg s.c.) reversed the 6,7-ADTN-induced delayed emptying but not the clonidine-induced delayed emptying. In addition, metoclopramide (5–10 mg/kg s.c.), but not haloperidol, increased gastric emptying in the absence of agonist.
• 5 In conclusion, these results show that dopamine and a-adrenoreceptors may be involved in the control of gastric emptying in the rat. However, it would appear that a2-adrenoreceptors are unlikely to be involved in the mechanism of action of metoclopramide. Although there is some evidence that peripheral dopamine receptors may be involved, the fact that metoclopramide significantly increased gastric emptying in the absence of 6,7-ADTN suggests that its dopamine receptor antagonist properties may contribute only in part towards its mechanism of action.

     

PHARMACOKINETICS OF SINGLE-DOSE I.V.MORPHINE IN NORMAL VOLUNTEERS AND PATIENTS WITH END-STAGE RENAL FAILURE

Morphine 0.125 mgkg^–1 was administered i.v. to 11 normalsubjects and nine patients with chronic renal failure requiringregular haemodialysis. Plasma morphine concentrations were measuredusing high pressure liquid chromatography (HPLC). Although therewas considerable individual variation in both groups, mean plasmaconcentrations of morphine were significantly higher in thepatients with renal failure for 15 min after administration.The decay of plasma concentration fitted a three-compartmentmamillary pharmacokinetic model in all subjects. Derived values(mean $ SEM) of T^x, volume of distribution of the second compartment(V₂), total volume of distribution at steady state ( V^ss1) andtransfer rate constant from the first to the second compartment(k₁₂) were significantly different between groups. Mean valuesof terminal elimination half-life (T⁷) and total body clearancewere similar in the two groups. It was concluded that eliminationof unchanged morphine is not impaired significantly in patientswith chronic renal failure, although accumulation of morphine-3-glucuronideprobably occurs. Although the pharmacological effect of morphineis not related temporally to plasma morphine concentrations,the higher values in patients with renal failure may be implicatedin their increased sensitivity to the drug     

消痔灵和强的松龙混合液治疗鼻息肉

0　引言　我科 1996 / 1998分别应用消痔灵与强的松龙混合液、消痔灵液、强的松龙液行鼻息肉内 ,鼻息肉蒂部注射治疗鼻息肉各 5 0例 ,并设对照组为鼻腔滴入及口服类固醇激素 5 0例 ,合计 2 0 0例 ,观察并对比其疗效 .1　对象和方法1.1　对象　男 12 8例 ,女 72例 ,年龄 8～ 78(平均 38)岁 ,病程 32 a～ 45 (平均 4.5 ) a.其中在本次治疗前做过一次鼻息肉摘除术后复发的 2 7例 ,做过 2次或 2次以上手术的 12例 .主要症状为鼻塞、流脓涕、头痛及嗅觉减退 .全部病例治疗前均行鼻窦 X线拍片 ,其中上颌窦炎 12 5例、筛窦炎 5 8例、蝶窦炎 2例、…     

CALCIUM PYROPHOSPHATE DEPOSITION DISEASE--INVOLVEMENT OF THE ACROMIOCLAVICULAR JOINT WITH PSEUDOCYST FORMATION

Two cases presenting with pseudocyst formation due to pyrophosphatearthropathy involving the acromioclavicular joint are described. KEY WORDS: Chondrocalcinosis, Pseudogout, Acromioclavicular joint     

HEIGHT, OCCUPATION AND BACK PAIN IN A NATIONAL PROSPECTIVE STUDY

Back pain is an important public health problem but there isa paucity of knowledge about risk factors and causal mechanisms.Previous studies have shown that tall men are more at risk ofback pain, although observations in women have been less consistent.This paper presents findings from a national longitudinal studyof 3262 men and women aged 43 yr. Standing height and sittingheight were related to 18-month reported prevalence of ‘sciatica,lumbago or severe backache’ in both men and women. Thepaper investigates explanations for these findings using previouslycollected data on childhood growth and detailed lifetime occupationalhistories. Neither greater susceptibility of tall men to heavylifting, nor the timing of growth, were able to account forthese relationships. To assess further the association betweenheight and back pain, information is needed on the relationshipbetween stature and characteristics of spinal structure. KEY WORDS: Longitudinal, British, Growth, Adults, Lifting, Spine     

HLA ASSOCIATIONS IN SUBJECTS WITH RHEUMATOID ARTHRITIS AND BRONCHIECTASIS BUT NOT WITH OTHER PULMONARY COMPLICATIONS OF RHEUMATOID DISEASE

We have examined HLA-DR, DQA and DQB variants in 72 controls,153 subjects with RA without extra-articular features and insubjects with the rheumatoid pulmonary complications of interstitialfibrosis (23) peripheral airways disease (13) and in 41 subjectswith RA and bronchiectasis. Subjects with RA alone showed theexpected association with HLA-DR4 (79%) but those with RA andco-existent pulmonary fibrosis were less likely to be DR4 positive(61%). No other HLA-DR variants were significantly increasedin the different disease groups. HLA which types serologicallyas DQw1 was increased in subjects with RA and peripheral airwaysdisease as compared to rheumatoid subjects with normal lungfunction, but these differences were not statistically significant.DQBI*0601 was increased in subjects with bronchiectasis withor without RA (but only significantly so in RA-BR subjects)DQBI*0301, DQBI*020l and DQAI*0501 frequencies were also increasedin subjects with RA and bronchiectasis as compared to thosewith RA alone. KEY WORDS: Rheumatoid arthritis, Pulmonary fibrosis, Obstructive airways disease, Bronchiectasis, HLA-DR, HLA-DQ, HLA-Dw, C4