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1.
Zootaxa ; 4766(2): zootaxa.4766.2.7, 2020 Apr 20.
Article in English | MEDLINE | ID: mdl-33056602

ABSTRACT

A new species of insular Bent-toed Gecko, Cyrtodactylus culaochamensis sp. nov. of the C. irregularis group is described from Cu Lao Cham Mountain, from Hon Lao Island, Hoi An City, Quang Nam Province, Cham Islands, central Vietnam. Cyrtodactylus culaochamensis sp. nov. is the sister species of C. pseudoquadrivirgatus from Ba Na Nui Chua from Danang City, central Vietnam. It differs from all congeners by having a maximum SVL of 79.8 mm (n=5); dark spots on the head edged in white; a fragmented nuchal loop; irregularly shaped, broad, completed or broken dorsal bands; 19-21 interorbital scales across the frontal bone; 28-32 scales between the eye and nostril; 45-50 rows of ventral scales between the ventrolateral folds; scattered, smooth tubercles; 20-22 irregular, longitudinal rows of weakly keeled tubercles at midbody between the ventrolateral folds; seven or eight precloacal pores in a chevron pattern in males; no enlarged femoral scales, no femoral pores; 13-15 subdigital lamellae on first toe; 20-23 subdigital lamellae on fourth toe; and very slightly enlarged subcaudal scales.


Subject(s)
Lizards , Animal Distribution , Animal Structures , Animals , Body Size , Ecosystem , Male , Vietnam
2.
Eur J Obstet Gynecol Reprod Biol ; 235: 30-35, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30780074

ABSTRACT

BACKGROUND: The British Society of Paediatric and Adolescent Gynaecology (BritSPAG) was created in 2000 with specific aims to include raising the profile of paediatric and adolescent gynaecology (PAG) within the United Kingdom (UK). The Society has since developed a set of clinical standards for all acute hospitals providing gynaecological services to enable successful provision of paediatric and adolescent gynaecology care. AIMS: To determine the depth of knowledge that obstetric and gynaecology trainees have with regards to the PAG services provided at their Hospital, reflecting how widely PAG services have had an impact on trainees. METHOD: The national survey was distributed to all deaneries in the UK for circulation to all their trainees via e mail during Nov 2017-March 2018. RESULTS: 28% of the trainees said there was a PAG clinic at their hospital, 46.9% did not have a clinic and 24.7% were unsure. 41.6% of the respondents were aware of BritSPAG, however only 10.4% were aware of the BritSPAG clinical standards for service planning with regards to PAG clinics. Nearly half were aware of the PAG specialist centre for their region but only 6.5% were aware of the BritSPAG UK map of services. A large majority (93.24%) didn't believe that trainees in O&G received adequate exposure to PAG in their training. CONCLUSION: This study represents the largest and first national survey to seek obstetric and gynaecology trainees' thoughts on the provision of PAG training in the UK today. Given that only 28% of trainees answering said that they were aware of a PAG clinic at their hospital, this indicates not only that many hospitals did not have a dedicated PAG clinic but more worryingly five of the trainees were not aware of the existence of a confirmed PAG clinic at their hospital, and therefore are potentially losing out on training opportunities. Disappointingly the results of our survey reveal that trainees in Obstetrics and Gynaecology still have very little experience or exposure to PAG during their training despite there being opportunities to do so.


Subject(s)
Gynecology/education , Health Knowledge, Attitudes, Practice , Maternal Health Services , Obstetrics/education , Students, Medical/psychology , Adolescent , Adolescent Medicine/methods , Adult , Child , Female , Gynecology/methods , Humans , Male , Middle Aged , Obstetrics/methods , Pediatrics/methods , Pregnancy , Qualitative Research , Surveys and Questionnaires , United Kingdom
3.
Zootaxa ; 4061(1): 1-17, 2016 Jan 04.
Article in English | MEDLINE | ID: mdl-27395475

ABSTRACT

A new species of Bent-toed Gecko, Cyrtodactylus gunungsenyumensis sp. nov. of the sworderi complex, is described from Hutan Lipur Gunung Senyum, Pahang, Peninsular Malaysia and is differentiated from all other species in the sworderi complex by having a unique combination of characters including a maximum SVL of 74.7 mm; low, rounded, weakly keeled, body tubercles; 34-40 paravertebral tubercles; weak ventrolateral body fold lacking tubercles; 38-41 ventral scales; an abrupt transition between the posterior and ventral femoral scales; 20-23 subdigital lamellae on the fourth toe; enlarged femoral scales; no femoral or precloacal pores; no precloacal groove; wide caudal bands; and an evenly banded dorsal pattern. Cyrtodactylus gunungsenyumensis sp. nov. is a scansorial, karst forest-adapted specialist endemic to the karst ecosystem surrounding Gunung Senyum and occurs on the vertical walls of the limestone towers as well as the branches, trunks, and leaves of the vegetation in the associated karst forest. Cyrtodactylus gunungsenyumensis sp. nov. is the seventh species of karst forest-adapted Cyrtodactylus and the sixteenth endemic species of karst ecosystem reptile discovered in Peninsular Malaysia in the last seven years from only 12 different karst forests. This is a clear indication that many species remain to be discovered in the approximately 558 isolated karst ecosystems in Peninsular Malaysia not yet surveyed. These data continue to underscore the importance of karst ecosystems as reservoirs of biodiversity and microendemism and that they constitute an important component of Peninsular Malaysia's natural heritage and should be protected from the quarrying interests of foreign industrial companies.


Subject(s)
Lizards/classification , Animal Distribution , Animal Structures/anatomy & histology , Animal Structures/growth & development , Animals , Body Size , Conservation of Natural Resources , Construction Industry , Ecosystem , Endangered Species , Female , Forests , Lizards/anatomy & histology , Lizards/genetics , Lizards/growth & development , Malaysia , Male , Organ Size , Phylogeny
4.
Zootaxa ; 3980(1): 106-26, 2015 Jun 26.
Article in English | MEDLINE | ID: mdl-26249941

ABSTRACT

An integrative taxonomic analysis of the distantly related Cyrtodactylus condorensis and intermedius species complexes of the Mekong Delta revealed that C. paradoxus is a junior synonym of C. condorensis and that C. thochuensis is a junior synonym of C. leegrismeri. Additionally, the analysis revealed that a cave-dwelling ecomorpholgy has evolved independently early on in the evolution of both complexes (represented by C. hontreensis in the intermedius complex and C. grismeri and C. eisenmani in the condorensis complex) and cave ecomorphs exist in sympatry-but not syntopy-with general scansorial ecomorphs. Multiple, recent, cyclical, glacioeustatic driven changes in sea levels across the Sunda Shelf are hypothesized to account for the evolution and distribution of the widely separated, conspecific insular populations of C. condorensis and C. leegrismeri. The independent evolution of cave ecomorphology is proposed to have been driven by competition avoidance. Habitat islands across the Mekong Delta are an important source of endemism and in need of protection.


Subject(s)
Animal Distribution , Caves , Lizards/classification , Animals , Ecosystem , Lizards/anatomy & histology , Lizards/genetics , Lizards/physiology , Phylogeny , Species Specificity , Thailand
5.
Zootaxa ; 3985(2): 203-18, 2015 Jul 10.
Article in English | MEDLINE | ID: mdl-26250030

ABSTRACT

A new, diminutive species of Rock Gecko Cnemaspis mahsuriae sp. nov. of the affinis group, is described from Gunung Raya on Pulau Langkawi, Kedah, Peninsular Malaysia and is differentiated from all other species in the affinis group by having a unique combination of characters including a maximum SVL of 36.6 mm; keeled subtibials and ventrals; 21-24 paravertebral tubercles; no tubercles in the lateral caudal furrows; caudal tubercles not encircling tail; no precloacal pores; 23-26 subdigital lamellae on the fourth toe; no white ocelli in the shoulder region; no yellow postscapular band; and faint yellow bars on the flanks. Cnemaspis mahsuriae sp. nov. is a forest-dwelling species living in close sympatry or paraptry with the insular endemic C. roticanai Grismer & Chan. The Langkawi Archipelago harbors a unique mix of Malaysian and Indochinese taxa and the frequency of new discoveries from this group of islands is increasing.


Subject(s)
Lizards/classification , Animal Distribution , Animal Structures/anatomy & histology , Animal Structures/growth & development , Animals , Body Size , Female , Lizards/anatomy & histology , Lizards/genetics , Lizards/growth & development , Malaysia , Male , Organ Size , Phylogeny
6.
Zootaxa ; 3948(1): 1-23, 2015 Apr 20.
Article in English | MEDLINE | ID: mdl-25947760

ABSTRACT

An integrative taxonomic analysis is used to identify and describe two new species of the agamid genus Bronchocela (Kuhl) from Peninsular Malaysia: an upland species B. shenlong sp. nov. from Bukit Larut, Perak in the Bintang Mountain Range and Parit Falls, Cameron Highlands, Pahang in the Titiwangsa Mountain Range and an insular species, B. rayaensis sp. nov., from Pulau Langkawi, Kedah off the northwest coast on the border with Thailand. Both species are diagnosed from each other and all other species of Bronchocela on the basis of body shape, scale morphology, and color pattern. The analysis also demonstrates the remarkable genetic similarity of B. cristatella (Kuhl) throughout 1120 km of its range from northern Peninsular Malaysia to western Borneo despite its highly variable coloration and pattern. The two new species are appended to a rapidly growing list of newly described lizard species (60 to date) from Peninsular Malaysia tallied within the last decade.


Subject(s)
Lizards/classification , Animal Distribution , Animal Structures/anatomy & histology , Animal Structures/growth & development , Animals , Body Size , Ecosystem , Female , Lizards/anatomy & histology , Lizards/genetics , Lizards/growth & development , Malaysia , Male , Organ Size , Phylogeny
7.
Zootaxa ; 3760: 539-52, 2014 Feb 04.
Article in English | MEDLINE | ID: mdl-24870104

ABSTRACT

A new species of the gekkonid Hemiphyllodactylus banaensis sp. nov. is described from Ba Na-Nui Chua Nature Reserve in central Vietnam. Previously included within H. yunnanensis, the new species is distinguished from all other congeners by having the unique combination of a maximum SVL of 48.2 mm in males and 51.0 mm in females; seven chin scales extending transversely from the union of the first and second infralabials and posterior margin of mental; enlarged postmental scales; 9-12 supralabials; 9-11 infralabials; 18-20 longitudinally arranged dorsal scales at midbody contained within one eye diameter; 20-21 precloacal and femoral pore-bearing scales contiguous in males and 0-20 contiguous pore-bearing precloacal scales in females; dorsal pattern on body composed of transverse blotches and two whitish stripes across shoulder extending to sacrum; postsacral mark whitish brown and bearing anteriorly projecting arms; and caecum and oviducts unpigmented.


Subject(s)
Lizards/anatomy & histology , Lizards/classification , Animals , Demography , Female , Lizards/genetics , Lizards/physiology , Male , Phylogeny , Species Specificity , Vietnam
8.
J Obstet Gynaecol ; 32(5): 413-8, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22663308

ABSTRACT

Vasa praevia can cause acute severe fetal haemorrhage prior to or during rupture of the membranes, contributing to perinatal morbidity and mortality. There are no large prospective studies relating to vasa praevia and there is no place for a randomised controlled trial as it would be ethically unjustifiable given the poor prognosis. There are no national guidelines for the management of vasa praevia. Identification of vasa praevia by the 3rd trimester of pregnancy warrants the offer of delivery by planned caesarean section to avoid the complications. This is essentially intuitive and logical rather than based on any randomised trials. A universal screening programme for vasa praevia is not currently supported by a robust evidence base; however, the role of prenatal diagnosis requires an informed debate, as high quality data may not be forthcoming, given the low evidence of the condition. Increasing awareness and understanding of the clinical situations can accumulate information, which identify and treat this tragic complication of childbirth.


Subject(s)
Prenatal Diagnosis , Vasa Previa/diagnosis , Cesarean Section , Female , Fetal Diseases/etiology , Gestational Age , Hemorrhage/etiology , Humans , Mass Screening , Perinatal Mortality , Pregnancy , Vasa Previa/therapy
9.
BJOG ; 117(13): 1643-50, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21078058

ABSTRACT

OBJECTIVE: The Paediatric and Adolescent Gynaecology service (PAG) at Kettering General Hospital is a designated service meeting the needs of children with gynaecological problems. National guidelines reinforce the fact that children should be seen within specific paediatric areas in hospital. We aim to review the role of such a service in the context of a British district general hospital. DESIGN: Retrospective review spanning 15 years. SETTING: The outpatient/inpatient service of a UK district general hospital. POPULATION: A total of 800 patients were included in the study. METHODS: We identified patients attending the PAG clinic between 1994 and 2009. Medical notes were reviewed individually. MAIN OUTCOME MEASURES: Demographics, referral source, presenting symptoms, examination findings, diagnosis, management, admissions and referrals to tertiary centres. RESULTS: In total, 86% of patients were referred from primary care. The age distribution was bimodal at 4 and 15 years of age: the average age was 10 years. Sixty percent of patients were followed-up, giving a total of 2023 appointments. The commonest presentations were vulvovaginitis (18%), labial adhesions (14%), abdominal pain (7%) and precocious puberty (6%). A total of 15% of patients were admitted, largely for planned procedures, of which vaginoscopy was the most frequent. CONCLUSIONS: The PAG service has enabled pathways for care that were previously non-existent, as well as the development of 'best practice'. The British Society for Paediatric and Adolescent Gynaecology has been seeking to develop a network of similar services at secondary and tertiary level throughout the UK. This approach should be encouraged and promoted by those in charge of healthcare policy and provider trusts in general.


Subject(s)
Adolescent Health Services/statistics & numerical data , Child Health Services/statistics & numerical data , Hospitals, District/statistics & numerical data , Hospitals, General/statistics & numerical data , Women's Health Services/statistics & numerical data , Adolescent , Child , Child, Preschool , England , Female , Genital Diseases, Female/therapy , Genitalia, Female/abnormalities , Humans , Infant , Menstruation Disturbances/therapy , Pregnancy , Pregnancy in Adolescence , Puberty, Precocious/therapy , Retrospective Studies , Sex Offenses , Urination Disorders/therapy , Vulvovaginitis/therapy
10.
J Bone Joint Surg Br ; 92(7): 958-62, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20595114

ABSTRACT

We describe the early results of a prospective study of 100 total ankle replacements (96 patients) at a single centre using the Mobility Total Ankle Replacement. At final review, six patients had died and five ankles (5%) had been revised, two by fusion and three by exchange of components. All remaining patients were reviewed at a minimum of three years. The mean follow-up was 43 months (4 to 63). The three-year survival was 97% (95% confidence interval (CI) 91 to 99). The four-year survival was 93.6% (95% CI 84.7 to 97.4). The portion of bony interface that was visible on plain radiograph was divided into 15 zones and a radiolucent line or osteolytic cavity was seen in one zone in 14 ankles. It was not seen in more than one zone. In five ankles it was > 10 mm in width. This study suggests that the early outcome of ankle replacement is comparable to that of other total joint replacements.


Subject(s)
Ankle Joint/surgery , Arthroplasty, Replacement/methods , Adult , Aged , Aged, 80 and over , Arthritis, Rheumatoid/surgery , Arthroplasty, Replacement/adverse effects , Epidemiologic Methods , Female , Humans , Joint Prosthesis , Male , Middle Aged , Osteoarthritis/surgery , Prosthesis Failure , Reoperation , Treatment Outcome
12.
J Bone Joint Surg Br ; 91(1): 69-74, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19092007

ABSTRACT

We describe the results of a randomised, prospective study of 200 ankle replacements carried out between March 2000 and July 2003 at a single centre to compare the Buechel-Pappas (BP) and the Scandinavian Total Ankle Replacement (STAR) implant with a minimum follow-up of 36 months. The two prostheses were similar in design consisting of three components with a meniscal polyethylene bearing which was highly congruent on its planar tibial surface and on its curved talar surface. However, the designs were markedly different with respect to the geometry of the articular surface of the talus and its overall shape. A total of 16 ankles (18%) was revised, of which 12 were from the BP group and four of the STAR group. The six-year survivorship of the BP design was 79% (95% confidence interval (CI) 63.4 to 88.5 and of the STAR 95% (95% CI 87.2 to 98.1). The difference did not reach statistical significance (p = 0.09). However, varus or valgus deformity before surgery did have a significant effect) (p = 0.02) on survivorship in both groups, with the likelihood of revision being directly proportional to the size of the angular deformity. Our findings support previous studies which suggested that total ankle replacement should be undertaken with extreme caution in the presence of marked varus or valgus deformity.


Subject(s)
Ankle Joint/surgery , Arthroplasty, Replacement/methods , Joint Prosthesis/standards , Prosthesis Design/standards , Talus/surgery , Adult , Aged , Aged, 80 and over , Ankle Joint/abnormalities , Ankle Joint/diagnostic imaging , Arthroplasty, Replacement/standards , Female , Humans , Male , Middle Aged , Osteoarthritis/diagnostic imaging , Osteoarthritis/physiopathology , Osteoarthritis/surgery , Polyethylene , Prospective Studies , Radiography , Talus/abnormalities , Talus/diagnostic imaging , Treatment Outcome , Young Adult
13.
J Bone Joint Surg Br ; 90(5): 605-9, 2008 May.
Article in English | MEDLINE | ID: mdl-18450626

ABSTRACT

We describe the medium-term results of a prospective study of 200 total ankle replacements at a single-centre using the Scandinavian Total Ankle Replacement. A total of 24 ankles (12%) have been revised, 20 by fusion and four by further replacement and 27 patients (33 ankles) have died. All the surviving patients were seen at a minimum of five years after operation. The five-year survival was 93.3% (95% confidence interval (CI) 89.8 to 96.8) and the ten-year survival 80.3% (95% CI 71.0 to 89.6). Anterior subluxation of the talus, often seen on the lateral radiograph in osteoarthritic ankles, was corrected and, in most instances, the anatomical alignment was restored by total ankle replacement. The orientation of the tibial component, as seen on the lateral radiograph, also affects the position of the talus and if not correct can hold the talus in an abnormal anterior position. Subtalar arthritis may continue to progress after total ankle replacement. Our results are similar to those published previously.


Subject(s)
Ankle Joint/surgery , Arthroplasty, Replacement/methods , Joint Prosthesis/standards , Osteoarthritis/surgery , Ankle Joint/diagnostic imaging , Arthroplasty, Replacement/standards , Follow-Up Studies , Humans , Osteoarthritis/diagnostic imaging , Prospective Studies , Radiography , Reoperation , Scandinavian and Nordic Countries , Statistics as Topic , Time Factors
14.
J Bone Joint Surg Br ; 89(5): 615-9, 2007 May.
Article in English | MEDLINE | ID: mdl-17540746

ABSTRACT

A consecutive series of 23 patients (25 ankles) with osteoarthritis of the ankle and severe varus or valgus deformity were treated by open arthrodesis using compression screws. Primary union was achieved in 24 ankles one required further surgery to obtain a solid fusion. The high level of satisfaction in this group of patients reinforces the view that open arthrodesis, as opposed to ankle replacement or arthroscopic arthrodesis, continues to be the treatment of choice when there is severe varus or valgus deformity associated with the arthritis.


Subject(s)
Ankle Joint/surgery , Arthrodesis/methods , Joint Deformities, Acquired/surgery , Osteoarthritis/surgery , Adult , Aged , Aged, 80 and over , Ankle Joint/diagnostic imaging , Ankle Joint/physiopathology , Arthrodesis/adverse effects , Arthrodesis/rehabilitation , Bone Screws , Female , Humans , Joint Deformities, Acquired/diagnostic imaging , Joint Deformities, Acquired/etiology , Male , Middle Aged , Osteoarthritis/complications , Osteoarthritis/diagnostic imaging , Patient Satisfaction , Radiography , Recovery of Function , Treatment Outcome
15.
J Bone Joint Surg Br ; 88(8): 1032-8, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16877602

ABSTRACT

Between 1999 and 2005, 23 failed total ankle replacements were converted to arthrodeses. Three surgical techniques were used: tibiotalar arthrodesis with screw fixation, tibiotalocalcaneal arthrodesis with screw fixation, and tibiotalocalcaneal arthrodesis with an intramedullary nail. As experience was gained, the benefits and problems became apparent. Successful bony union was seen in 17 of the 23 ankles. The complication rate was higher in ankles where the loosening had caused extensive destruction of the body of the talus, usually in rheumatoid arthritis. In this situation we recommend tibiotalocalcaneal arthrodesis with an intramedullary nail. This technique can also be used when there is severe arthritic change in the subtalar joint. Arthrodesis of the tibiotalar joint alone using compression screws was generally possible in osteoarthritis because the destruction of the body of the talus was less extensive. Tibiotalocalcaneal arthrodesis fusion with compression screws has not been successful in our experience.


Subject(s)
Ankle Joint/surgery , Arthrodesis/methods , Arthroplasty, Replacement/methods , Foot Joints/surgery , Adult , Aged , Ankle Joint/diagnostic imaging , Arthritis, Rheumatoid/diagnostic imaging , Arthritis, Rheumatoid/surgery , Bone Nails , Bone Screws , Calcaneus , Female , Foot Joints/diagnostic imaging , Humans , Male , Middle Aged , Osteoarthritis/diagnostic imaging , Osteoarthritis/surgery , Postoperative Complications , Prosthesis Design , Prosthesis Failure , Radiography , Reoperation , Subtalar Joint/pathology , Talus , Tibia , Treatment Failure
16.
J Bone Joint Surg Br ; 85(3): 334-41, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12729104

ABSTRACT

Between 1993 and 2000 we implanted 200 cementless, mobile-bearing STAR total ankle replacements. None was lost to follow-up for reasons other than the death of a patient. The mean follow-up was for 46 months (24 to 101). A complication requiring further surgery developed in eight ankles and 14 were revised or fused. The cumulative survival rate at five years was 92.7% (95% CI 86.6 to 98.8) with time to decision to revision or fusion as an endpoint. The most frequent complications were delayed wound healing and fracture of a malleolus. These became less common with experience of the operation. The radiological appearance of the interface of the tibial implant was significantly related to its operative fit and to the type of bioactive coating.


Subject(s)
Ankle Joint/surgery , Arthritis/surgery , Arthroplasty, Replacement/methods , Joint Prosthesis , Aged , Ankle Joint/diagnostic imaging , Arthritis/physiopathology , Arthroplasty, Replacement/adverse effects , Female , Follow-Up Studies , Foot Bones/injuries , Fractures, Bone/etiology , Fractures, Bone/surgery , Humans , Male , Middle Aged , Pain/etiology , Pain/surgery , Prosthesis Design , Radiography , Range of Motion, Articular , Recovery of Function , Survival Analysis , Treatment Outcome
17.
J Pharmacol Exp Ther ; 295(1): 337-45, 2000 Oct.
Article in English | MEDLINE | ID: mdl-10991999

ABSTRACT

The purpose of this study was to evaluate the effects of a novel neuroactive steroid, Co 2-6749 (GMA-839; WAY-141839; 3alpha, 21-dihydroxy-3beta-trifluoromethyl-19-nor-5beta-pregnan-20-one), on gamma-aminobutyric acid(A) receptors in vitro and to define its anxiolytic-like effects and side effect profile in vivo. Co 2-6749 fully inhibited [(35)S]t-butylbicyclophosphorothionate binding in rat brain cortical membranes with an IC(50) value of 230 nM and in human gamma-aminobutyric acid(A) receptor subunit combinations of alpha1beta2gamma2L, alpha2beta2gamma2L, alpha3beta2gamma2L, alpha4beta3gamma2L, alpha5beta2gamma2L, and alpha6beta3gamma2L receptors (IC(50) values of 200, 200, 96, 2300, 210, and 2000 nM). Rats were trained in a Geller-Seifter operant conflict paradigm. Co 2-6749 caused a dose-related increase in punished responding with a minimum effective dose of 1.6 mg/kg, p.o., a wide therapeutic index relative to a decrease in unpunished responding and relative to ataxia, and no tolerance. Additionally, ethanol caused less than a 2-fold shift to the left in the dose-response function of Co 2-6749 in the rotorod procedure in rats. In a pigeon conflict paradigm, punished responding was maximally increased to 784% of vehicle control by 30 mg/kg, p.o., with a 2-h duration and no effect on unpunished responding at this dose. Similarly, punished responding in squirrel monkeys was maximally increased to 1774% of control by 10 mg/kg, p.o., with no effect on unpunished responding at this dose. With robust anxiolytic-like activity across species, a large separation between anxiolytic-like effects and sedation/ataxia, a minimal interaction with ethanol, a lack of tolerance, and apparent oral bioavailability, Co 2-6749 makes an ideal candidate for development as a novel anxiolytic drug.


Subject(s)
Anti-Anxiety Agents/pharmacology , GABA Modulators/pharmacology , Pregnanolone/analogs & derivatives , Receptors, GABA-A/drug effects , Alprazolam/pharmacology , Animals , Bridged Bicyclo Compounds, Heterocyclic/metabolism , Cell Line , Columbidae , Conflict, Psychological , Humans , Male , Motor Activity/drug effects , Pregnanolone/pharmacology , Rats , Rats, Sprague-Dawley , Saimiri
20.
Psychopharmacology (Berl) ; 145(2): 205-12, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10463322

ABSTRACT

RATIONALE AND OBJECTIVES: The present study was designed to assess possible abuse-related effects of the endogenous neuroactive steroid pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one) and the orally bioavailable, water-soluble neuroactive steroid pro-drug Co 8-7071 (3alpha,21-dihydroxy-3beta-trifluoromethyl-5beta-pregnan-20- one, 21-hemisuccinate). METHODS: Four rhesus monkeys were prepared with chronic intravenous (i.v.) catheters and trained to press a lever under a ten-response fixed-ratio (FR) schedule of methohexital injection (0.1 mg/kg per injection). Three rhesus monkeys were trained to discriminate intragastric infusions of pentobarbital (10 mg/kg) from saline infusions under a FR5 schedule of stimulus-shock termination. RESULTS: At least two doses of pregnanolone (0.003-0.1 mg/kg per injection) maintained injections per session above saline levels in the four monkeys tested, whereas Co 8-7071 (0.01-1.0 mg/kg per injection) maintained injections per session above saline levels in two of four monkeys at relatively low levels of injections per session. In rhesus monkeys trained to discriminate pentobarbital, i.v. pregnanolone injections (0.1-1.7 mg/kg, 5-min presession) dose-dependently reproduced the discriminative stimulus effects of pentobarbital in all monkeys tested. Intravenous administration of Co 8-7071 (1-10 mg/kg, 5-min presession) resulted in a dose-dependent increase to >80% pentobarbital-appropriate responding in two of three monkeys tested. Following intragastric infusions of Co 8-7071 (1.0-30 mg/kg), > or =80% pentobarbital-appropriate responding occurred in one out of three monkeys at 10 mg/kg when administered 60 min before the session. When administered 120 min before the session, however, 10-30 mg/kg Co 8-7071 reproduced the discriminative stimulus effects of pentobarbital in each of the three monkeys tested. CONCLUSIONS: These data demonstrate barbiturate-like abuse-related effects that differed between two pregnane steroids. Whereas pregnanolone functioned as a reinforcer, suggesting that this compound has abuse potential, Co 8-7071 did not, despite having pentobarbital-like discriminative effects.


Subject(s)
Discrimination Learning/drug effects , Pregnanolone/analogs & derivatives , Pregnanolone/pharmacology , Prodrugs/pharmacology , Reinforcement, Psychology , Animals , Behavior, Animal/drug effects , Dose-Response Relationship, Drug , Female , Macaca mulatta , Male , Pregnanolone/administration & dosage , Self Administration
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