Polymorphisms in type 2 deiodinase are not associated with well-being, neurocognitive functioning, and preference for combined thyroxine/3,5,3'-triiodothyronine therapy

INTRODUCTION: Some patients on levothyroxine replacement display significant impairment in psychological well-being, compared with sex- and age-matched controls. Levothyroxine-treated patients can be assumed to derive T3 exclusively from deiodination of T4, which, in the central nervous system, is regulated by type II deiodinase (DII). OBJECTIVE: We investigated whether two recently identified polymorphisms in the DII gene (DII-ORFa-Gly3Asp and DII-Thr92Ala) are determinants of well-being and neurocognitive functioning and associated with a preference for replacement with a combination of T3 and T4. METHODS: Genotypes for both polymorphisms were determined in 141 patients with primary autoimmune hypothyroidism, adequately treated with levothyroxine monotherapy and participating in a randomized clinical trial comparing T4 therapy with T4/T3 combination therapy. Questionnaires on well-being and neurocognitive tests were performed at baseline. RESULTS: Allele frequencies in patients with primary hypothyroidism were similar to those of healthy blood bank donors (32.0 vs. 33.9% for DII-ORFa-Gly3Asp and 40.4 vs. 38.8% for DII-Thr92Ala). DII polymorphisms were not associated with measures of well-being, neurocognitive functioning, or preference for combined T4/T3 therapy. CONCLUSION: The DII-ORFa-Gly3Asp and DII-Thr92Ala polymorphisms do not explain differences in well-being, neurocognitive functioning, or appreciation of T4/T3 combination therapy in patients treated for hypothyroidism.     

The role of lipid,free radical initiator,and oxygen on the kinetics of lipid peroxidation

The relationship between the concentration of unsaturated lipid, free radical initiator, and oxygen concentration on the kinetics of lipid peroxidation was determined. The rate of lipid peroxidation was studied with the thiobarbituric acid (TBA), diene conjugation (DC), and ferrithiocyanate (Fe-SCN) methods. The rate of peroxidation was half-order with respect to unsaturated lipid, initiator, and oxygen. The half-order relationship could be expressed as: $\text{rate}\text{= (}\text{fk}{}_1\text{k}{}_2\text{k}{}_3\text{k}{}_6{}^{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}\text{(}\text{azobisisobutyronitrile}\text{)}{}^{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}$$\text{(}\text{RH}{}^{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}\text{(}\text{O}{}_2\text{)}{}^{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}$. The half-order relationship was found with linoleic (18:2), linolenic (18:3), and arachidonic (20:4) acids. A linear relationship existed between the logarithm of unsaturation and the rate of peroxidation. No peroxidation of linolenic acid was indicated when the DC method was employed, but was when the TBA and Fe-SCN methods were used.     

Vibration disappearance threshold may be raised by measuring it

The influence of duration and intensity of the initial level of vibration on vibration perception threshold was studied in 15 healthy young subjects (aged 27.9 ± 7.6 years) with a Vibrameter (Somedic AB Sweden).

The threshold for increasing vibration corresponded well to the normal values published by the manufacturer. The thresholds for decreasing vibration were measured with three different starting conditions: starting from a low level of vibration, a high level, and from a low level sustained for one minute. Higher intensity and longer duration of the initial vibration raised the disappearance threshold significantly. Vibration disappearance thresholds can be influenced by measuring them. As a result, the investigation of the vibration sense calls for strict control over intensity and duration of the stimuli.     

Disordered recognition of facial identity and emotions in three Asperger type autists

In this report we aim to explore severe deficits in facial affect recognition in three boys all of whom meet the criteria of Asperger's syndrome (AS), as well as overt prosopagnosia in one (B) and covert prosopagnosia in the remaining two (C and D). Subject B, with a familially-based talent of being highly gifted in physics and mathematics, showed no interest in people, a quasi complete lack of comprehension of emotions, and very poor emotional reactivity. The marked neuropsychological deficits were a moderate prosopagnosia and severely disordered recognition of facial emotions, gender and age. Expressive facial emotion, whole body psychomotor expression and speech prosody were quasi absent as well. In all three boys these facial processing deficits were more or less isolated, and general visuospatial functions, attention, formal language and scholastic performances were normal or even highly developed with the exception of deficient gestalt perception in B. We consider the deficient facial emotion perception as an important pathogenetic symptom for the autistic behaviour in the three boys. Prosopagnosia, the absent facial and bodily expression, and speech prosody were important but varying co-morbid disorders. The total clinical picture of non-verbal disordered communication is a complex of predominantly bilateral and/or right hemisphere cortical deficits. Moreover, in B, insensitivity to pain, smells, noises and internal bodily feelings suggested a more general emotional anaesthesia and/or a deficient means of expression. It is possible that a limbic component might be involved, thus making affective appreciation also deficient. Accepted: 18 January 2000     

Combined therapy with levothyroxine and liothyronine in two ratios, compared with levothyroxine monotherapy in primary hypothyroidism: a double-blind, randomized, controlled clinical trial

Controversy remains about the value of combined treatment with levothyroxine (LT4) and liothyronine (LT3), compared with LT4 alone in primary hypothyroidism. We compared combined treatment with LT4 and LT3 in a ratio of 5:1 or 10:1 with LT4 monotherapy. We conducted a double-blind, randomized, controlled trial in 141 patients (18-70 yr old) with primary autoimmune hypothyroidism, recruited via general practitioners. Inclusion criteria included: LT4 treatment for 6 months or more, a stable dose for 6 wk or more, and serum TSH levels between 0.11 and 4.0 microU/ml (mU/liter). Randomization groups were: 1) continuation of LT4 (n = 48); 2) LT4/LT3, ratio 10:1 (n = 46); and 3) LT4/LT3, ratio 5:1 (n = 47). Subjective preference of study medication after 15 wk, compared with usual LT4, was the primary outcome measure. Secondary outcomes included scores on questionnaires on mood, fatigue, psychological symptoms, and a substantial set of neurocognitive tests. Study medication was preferred to usual treatment by 29.2, 41.3, and 52.2% in the LT4, 10:1 ratio, and 5:1 ratio groups, respectively (chi2 test for trend, P = 0.024). This linear trend was not substantiated by results on any of the secondary outcome measures: scores on questionnaires and neurocognitive tests consistently ameliorated, but the amelioration was not different among the treatment groups. Median end point serum TSH was 0.64 microU/ml (mU/liter), 0.35 microU/ml (mU/liter), and 0.07 microU/ml (mU/liter), respectively [ANOVA on ln(TSH) for linear trend, P < 0.01]. Mean body weight change was +0.1, -0.5, and -1.7 kg, respectively (ANOVA for trend, P = 0.01). Decrease in weight, but not decrease in serum TSH was correlated with increased satisfaction with study medication. Of the patients who preferred combined LT4/LT3 therapy, 44% had serum TSH less than 0.11 microU/ml (mU/liter). Patients preferred combined LT4/LT3 therapy to usual LT4 therapy, but changes in mood, fatigue, well-being, and neurocognitive functions could not satisfactorily explain why the primary outcome was in favor of LT4/LT3 combination therapy. Decrease in body weight was associated with satisfaction with study medication.     

Elimination of bacteria from human semen during sperm preparation using density gradient centrifugation with a novel tube insert

The occurrence of bacteria in sperm samples intended for in vitro fertilisation can compromise the outcome of assisted reproductive techniques. Effective semen processing procedures should therefore be implemented to remove bacteria from semen. Unfortunately, technique failure does occur whereby bacteria can be found in processed sperm preparations. To improve the effectiveness of semen processing, a novel centrifuge tube insert was developed to facilitate the layering of density gradients and semen, and to prohibit the re‐infection of purified sperm pellets. The purpose of this study was to: (i) determine the prevalence and type of bacteria present in semen of patients participating in the Unit’s assisted reproduction program and (ii) evaluate the effectiveness of density gradient centrifugation with the novel tube insert, for the elimination of bacteria and yeast from spiked human semen samples. A survey in 2007–2010 indicated that 50% of semen samples were found to have positive bacterial cultures. Semen processing by means of density gradient centrifugation with the novel tube insert eliminated significantly more in vitro derived (spiked) bacteria and yeast from semen compared to processing without the insert (P < 0.004). Therefore, it is highly recommended that the centrifuge tube insert, ProInsert?, be incorporated into assisted reproductive programs.     

The influence of sera, follicular fluids and seminal plasma on human sperm-zona pellucida binding

The purpose of this study was to assess the influence of male, female and fetal cord sera, follicular fluid, and seminal plasma on human sperm-zona pellucida binding, using the hemizona assay. Steroids, gonadotrophins, growth hormone and prolactin concentrations in follicular fluid and sera were also analysed. The influence of follicular fluid (10 or 50%, v/v) and sera (10%) on sperm-zona pellucida binding was investigated by supplementing the sperm processing medium as well as the sperm-hemizona incubation medium. Different seminal plasma concentrations (1 or 10%) were added to the sperm-hemizona incubation medium. Supplementation with 10% day 3 donor serum was used as a control throughout experimentation. Although supplementation with male sera and fetal cord serum exerted a stimulatory effect (36 and 90% respectively; P < 0.029) on sperm-zona pellucida binding, hemizona indices obtained with addition of male sera, fetal cord serum and sera obtained from sub-fertile in-vitro fertilization (IVF) patients on day 12 of their menstrual cycle did not differ significantly (P > 0.05). Final progesterone concentrations in sperm-zona pellucida incubation media (10% follicular fluid supplementation), which ranged from 0.788 to 3.85 microg/ml, enhanced sperm binding to the zonae by >100% (P < 0.02). The utilization of follicular fluid (10%) as a natural physiological stimulus to enhance sperm-zona pellucida binding in an IVF setting is recommended. The presence of seminal plasma in the spermzona pellucida incubation media showed no beneficial effect on the binding ability of sperm, and can be viewed as an unfavourable substance in the proximity of the oocyte.