Biomedical subjects

A Hofer

Publications and source records attributed to A Hofer.

At least 19 recordsLinked to original sources

PubMed2006

A recombinant human enzyme for enhanced interstitial transport of therapeutics.

Subcutaneously injected therapeutics must pass through the interstitial matrix of the skin in order to reach their intended targets. This complex, three-dimensional structure limits the type and quantity of drugs that can be administered by local injection. Here we found that depolymerization of the viscoelastic component of the interstitial matrix in animal models with a highly purified recombinant human hyaluronidase enzyme (rHuPH20) increased the dispersion of locally injected drugs, across a broad range of molecular weights without tissue distortion. rHuPH20 increased infusion rates and the pattern and extent of appearance of locally injected drugs in systemic blood. In particular, rHuPH20 changed the pharmacokinetic profiles and significantly augmented the absolute bioavailability of locally injected large protein therapeutics. Importantly, within 24 h of injection, the interstitial viscoelastic barriers were restored without histologic alterations or signs of inflammation. rHuPH20 may function as an interstitial delivery enhancing agent capable of increasing the dispersion and bioavailability of coinjected drugs that may enable subcutaneous administration of therapeutics and replace intravenous delivery.

Adenoviridae↗

PubMed2006

The sepiapterin reductase gene region reveals association in the PARK3 locus: analysis of familial and sporadic Parkinson's disease in European populations.

BACKGROUND: Parkinson's disease is a genetically complex disease with mixed mode of inheritance. Recently, a haplotype across the sepiapterin reductase (SPR) gene, which is located in the PARK3 linkage region, was shown to modulate age of onset of Parkinson's disease in sibships from North America. OBJECTIVE: To make a thorough assessment of the SPR gene region in sporadic Parkinson's disease. METHODS: A linkage study in 122 European sibship families with five microsatellite and 17 single nucleotide polymorphism (SNP) markers in and around the SPR gene region, and an association analysis in 340 sporadic cases of Parkinson's disease and 680 control subjects from Germany with 40 SNPs. Linkage was evaluated by non-parametric linkage scores and genotypic or haplotype association was tested by regression analysis, assuming different risk effect models. RESULTS: Significant LOD scores between 2 and 3 were obtained at the two SPR-flanking markers D2S2110 and D2S1394 and seven SNP markers around the SPR gene. We found the previously reported promoter SNP rs1876487 also significantly associated with age of onset in our sib pair families (p-value 0.02). One strong linkage disequilibrium (LD) block of 45 kb including the entire SPR gene was observed. Within this LD block all 14 inter-correlated SNPs were significantly associated with Parkinson's disease affection status (p-value 0.004). CONCLUSIONS: DNA polymorphisms in a highly intercorrelated LD block, which includes the SPR gene, appear to be associated with both sporadic and familial Parkinson's disease. This confirms a previous study showing that SPR potentially modulates the onset of or risk for Parkinson's disease.

Age of Onset↗

PubMed2006

Cs*He(n) exciplexes in solid 4He.

We present a theoretical and experimental study of the laser-induced formation process and of the emission spectra of Cs*He(n) exciplexes in the hcp and bcc phases of solid helium. Two different exciplex molecules are detected: a linear triatomic Cs*He2, which can exist in two electronic states: APi(1/2) and BPi(3/2), and a larger complex, where six or seven He atoms form a ring around a single cesium atom in the 6P(1/2) state. A theoretical model is presented, which allows the interpretation of the experimentally observed spectra.

Journal Article↗

PubMed2006

Efficacy of 8-methoxypsoralen vs. 5-methoxypsoralen plus ultraviolet A therapy in patients with mycosis fungoides.

BACKGROUND: Psoralen plus ultraviolet (UV) A (PUVA) is the standard treatment for early stage mycosis fungoides (MF). When 8-methoxypsoralen (8-MOP) is used in PUVA therapy, it often produces intolerance reactions such as nausea, vomiting and headache. OBJECTIVES: To investigate whether 5-methoxypsoralen (5-MOP) is a safe and effective alternative to 8-MOP in PUVA therapy for MF. METHODS: A retrospective database search and chart review was done to identify patients with MF who received PUVA with either 5-MOP or 8-MOP as initial monotherapy at our institution. Between 1990 and 2004, 14 patients [seven men and seven women; mean age 70 years, range 51-82; National Cancer Institute disease stages IA (n = 6) and IB (n = 8)] received 5-MOP, and 24 patients [21 men and three women; mean age 58 years, range 28-89; disease stages IA (n = 11), IB (n = 12) and IIB (n = 1)] received 8-MOP. RESULTS: Twelve of 14 patients (86%) in the 5-MOP group and 22 of 24 (92%) in the 8-MOP group had a complete response to PUVA. These two subgroups of complete responders did not differ significantly in terms of PUVA therapy duration, number of treatments or cumulative UVA dose. They also did not differ significantly in terms of relapse-free rate [8% (one of 12) vs. 23% (five of 22)] or time to relapse [17 months (range 4-31) vs. 14 months (range 4-33)]. Moreover, PUVA maintenance therapy with either 5-MOP or 8-MOP in a subset of patients [26% (nine of 34)] did not affect long-term relapse-free status either. CONCLUSIONS: 5-MOP and 8-MOP have comparable therapeutic efficacy when used in PUVA therapy for MF.

5-Methoxypsoralen↗

PubMed2006

The efficacy of excimer laser (308 nm) for vitiligo at different body sites.

BACKGROUND: The treatment with XeCl-excimer laser generated 308-nm UVB radiation has shown promising results in patients with vitiligo. OBJECTIVE: In this controlled, prospective trial we studied the primary efficacy (start and grade of repigmentation) and patient's satisfaction of XeCl-excimer laser for treatment of vitiligo patches at different body sites and re-evaluated the achieved repigmentation 12 months after the end of therapy. METHODS: Twenty-five patients with generalized or localized vitiligo with a total of 85 lesions at different body sites were enrolled in this study. Vitiligo patches were treated with 308-nm XeCl-excimer laser 3 times a week for 6 to 10 weeks. The overall repigmentation grade of each treated lesion was evaluated once a week on a 5 point scale rating from 0 (no repigmentation), 1 (1-5%), 2 (6-25%), 3 (26-50%), 4 (51-75%), to 5 (76-100%). RESULTS: Twenty-four patients completed the study. Within 6 to 10 weeks of treatment 67% of the patients (16/24) developed follicular repigmentation of at least one of their vitiligo lesions. Lesion repigmentation started after a mean of 13 treatments in lesions located on the face, trunk, arm, and/or leg (high-responder location), and after a mean of 22 treatments in lesions located on the elbow, wrist, dorsum of the hand, knee, and/or dorsum of the foot (low-responder location). Untreated control lesions and lesions located on the fingers did not achieve any repigmentation. After 10 weeks of treatment repigmentation of more than 75% was found in 25% (7/28) of lesions of the high-responder location group versus 2% (1/43) of lesions of the low-responder location group. In most cases, laser-induced repigmentation was persistent, as determined 12 months after the end of treatment. CONCLUSIONS: 308-nm excimer laser is an effective modality for the treatment of vitiligo. However, similar to other non-surgical treatment modalities, the therapeutic effect is mainly dependent on the location of vitiligo lesions.

Adolescent↗

PubMed2006

Paired comparison of bathwater versus oral delivery of 8-methoxypsoralen in psoralen plus ultraviolet: A therapy for chronic palmoplantar psoriasis.

BACKGROUND: Both bath psoralen plus ultraviolet A (PUVA) and oral PUVA with 8-methoxypsoralen (8-MOP) have been successfully used for the treatment of recalcitrant palmoplantar psoriasis. This trial was designed to assess the efficacy and side effects of the different treatment modalities in a randomized half-side comparison. METHODS: Eight patients with moderate-to-severe psoriasis on soles (n = 6) and/or palms (n = 8) were randomly assigned to receive bath PUVA treatment on one side and oral PUVA on the other. Initial treatment dose was 50% of the minimal phototoxic dose evaluated for bath PUVA and oral PUVA. Treatment was given three times a week for 4 weeks. Before treatment and every week a severity index (SI) was assessed by summing the scores of erythema, infiltration, scaling and vesicles evaluated on a scale from 0 to 4. After 4 weeks of treatment the half-side trial was finished and the treatment was continued on both sides with the more effective treatment regimen. RESULTS: Both bath PUVA and oral PUVA achieved a reduction of the mean initial SI from 5.9 (95% confidence intervals (CI) 4.5-8.0) to 3.3 (1.8-6.0) (44% SI reduction, P < 0.005, Student's paired t-test) and 6.0 (5.0-7.8) to 2.9 (1.8-4.0) (52% SI reduction; P < 0.005), respectively. The statistical comparison of the entire 4-week study period revealed a significant better effect in lesions treated with oral PUVA compared with bath PUVA (P = 0.033). However, at 4 weeks, there was no significant difference between the achieved SI reduction of oral PUVA and bath PUVA. Systemic side effects (nausea and/or dizziness) were only observed after oral PUVA. CONCLUSION: This study gives evidence that in the first 4 treatment weeks oral PUVA is slightly more effective than bath PUVA but the former has more systemic side effects.

Adult↗

PubMed2006

Analysis of longevity and exterior traits on Large White sows in Switzerland.

Records of length of productive life, from first farrowing to culling, of 16,464 Large White purebred sows from SUISAG were studied using survival analysis. The major aims of the study were to model the risk of culling within parity and to assess the influence of exterior traits, such as the number of teats or feet and leg scores, on culling. Culling was concentrated at the first day after each farrowing or at the first day after weaning. Weaning itself was mostly between 21 and 49 d after farrowing, with an average weaning age of 35 d. Because of the definition of culling date used, there was practically no risk of culling from these periods. The culling rates at different periods suggested a modeling of the baseline hazard function within parity instead of over the entire productive life of the animals. A piecewise Weibull function and a simple graphical method to validate its adequacy were proposed for sow longevity analysis. The risk of culling increased with older parities (P < 0.001) and with decreasing litter size at weaning (P < 0.001). The exterior traits analyzed (number of teats, and feet and leg scores, on a scale from 1 to 7) had a moderate effect on the risk of culling compared with other factors but were still influential on survival, productive life expectancy, and annual replacement rate. Sows with less than 13 good teats had 1.35 times greater risk of being culled than sows with more good teats (P < 0.05). Sows with an X-O rear leg score of 2 had 1.4 times greater risk of being culled than sows with an intermediate score of 4 (P < 0.05). Sows at the optimum score of 4 for the size of inner claws of the rear leg had 0.83 times less risk of being culled (P < 0.01) than sows with scores of 2 and 3. Furthermore, when a phenotypic index for feet and legs was used to group these variables, the effect was highly significant (P < 0.001). Therefore, a means to improve longevity is through phenotypic selection of replacement gilts based on exterior traits: gilts with 13 or less good teats or with extreme feet and leg scores should be culled. From a genetic point of view, sows with the best value in the current index for exterior traits had a lower risk of culling (P < 0.01), and therefore, it is possible to obtain a response for sow longevity via indirect selection for exterior traits. From 1999 to 2003, the trend has been to eliminate extreme animals on exterior traits. This may partly explain the improvement of sow length of productive life longevity from 560 d in 2000 to nearly 710 d in 2003 observed in the data set.

Animal Husbandry↗

PubMed2005

Discovery of dumbbell-shaped Cs*Hen exciplexes in solid 4He.

We have observed several new spectral features in the fluorescence of cesium atoms implanted in the hcp phase of solid helium following laser excitation to the 62P states. Based on calculations of the emission spectra using semiempirical Cs-He pair potentials the newly discovered lines can be assigned to the decay of specific Cs*Hen exciplexes: an apple-shaped Cs(APi3/2)He2 and a dumbbell-shaped Cs(APi1/2)Hen exciplex with a well-defined number n of bound helium atoms. While the former has been observed in other environments, it was commonly believed that exciplexes with n>2 might not exist. The calculations suggest Cs(APi1/2)He7 to be the most probable candidate for that exciplex, in which the helium atoms are arranged on a ring around the waist of the dumbbell-shaped electronic density distribution of the cesium atom.

Journal Article↗

PubMed2005

Monitoring of selective antegrade cerebral perfusion using near infrared spectroscopy in neonatal aortic arch surgery.

BACKGROUND AND OBJECTIVE: To prevent neurological complications, low-flow antegrade cerebral perfusion (ACP) is used during repair of complex congenital heart defects. To overcome technical problems, continuous monitoring of cerebral blood flow and oxygenation is mandatory. The aim of the study was to evaluate the effect of different ACP flow rates on cerebral oxygen saturation obtained by near infrared spectroscopy. METHODS: Ten consecutive neonates undergoing Norwood stage I were included. In addition to near infrared spectroscopy (Invos 5100; Somanetics Corp., USA) on both hemispheres, mean arterial pressure and transcranial Doppler flow velocity were measured continuously and arterial and jugular venous oxygen saturation intermittently. Cerebral oxygen extraction ratio was calculated. Measurement points were obtained after starting bypass, during ACP with flow rates of 30, 20 and 10 mL kg(-1) min(-1) and immediately after ACP. ANOVA and Tukey-Kramer multiple comparison test were used for statistics. RESULTS: The near infrared spectroscopy signal could be obtained in all children at all measurement points, whereas transcranial Doppler failed in 1 neonate at a flow rate of 30 mL kg(-1)min(-1), in 3 neonates at 20 mL kg(-1) min(-1) and in 4 neonates at 10 mL kg(-1)min(-1). With the reduction of flow there was a significant decrease of cerebral oxygen saturation on both hemispheres (right: 78+/-8 to 72+/-9 and 66+/-8, P < 0.001; left: 71+/-7 to 65+/-7 and 60+/-7, P < 0.001), of jugular venous oxygen saturation (94+/-6 to 89+/-13 and 83+/-15, P < 0.001) and a significant increase in oxygen extraction ratio (9.1+/-8 to 14.8+/-14 and 21+/-16, P < 0.001) respectively, for 30, 20, 10 mL kg(-1)min(-1). CONCLUSION: Near infrared spectroscopy reliably detects flow alterations during ACP with profound hypothermia.

Anesthesia, General↗

PubMed2005

Optimal weekly frequency of 308-nm excimer laser treatment in vitiligo patients.

BACKGROUND: Recently the beneficial effect of excimer laser treatment has been reported for patients with vitiligo. The influence of treatment frequency on this effect is not clear. OBJECTIVES: To determine the optimal frequency of 308-nm excimer laser therapy for vitiligo. METHODS: In this prospective, university-based hospital study over 12 weeks we enrolled 14 patients. Each had at least three stable vitiligo lesions in the same body area. The three stable vitiligo lesions in each subject were randomly assigned to receive excimer laser treatment once (1 x), twice (2 x) and three times (3 x) weekly, respectively. The initial ultraviolet (UV) dose was 50 mJ cm(-2) less than the 308-nm minimal erythematous dose in vitiligo skin. The UV dose was increased at each treatment session according to the erythematous response to the previous treatment. RESULTS: Thirteen subjects were treated for at least 6 weeks; seven were treated for all 12 weeks. At 6 weeks, the repigmentation rates for treated lesions were 8% (1/13) after 1 x weekly treatment, 23% (3/13) after 2 x weekly treatment and 62% (8/13) after 3 x weekly treatment (P = 0.0134; 3 x vs. 1 x weekly); at 12 weeks, these rates were 46% (6/13), 62% (8/13) and 69% (9/13), respectively (P = NS; 3 x vs. 1 x weekly). Repigmentation initiation correlated with treatment number, regardless of frequency (P = NS). As shown by Kaplan-Meier analysis, repigmentation occurred earliest in the most frequently treated lesions (P = 0.0336). At 12 weeks, the projected repigmentation rates for 1 x, 2 x and 3 x weekly treatment approached each other (60%, 79% and 82%, respectively); the mean repigmentation grades (on a scale of 0-5) for 1 x, 2 x and 3 x weekly treatment were 1.7, 2.4 and 3.3, respectively (P = 0.018; 3 x vs. 1 x weekly). Laser-induced repigmentation persisted in most cases over the entire follow-up of 12 months after the end of treatment. CONCLUSIONS: 308-nm excimer laser therapy is effective against vitiligo. Although repigmentation occurs fastest with 3 x weekly treatment, the ultimate repigmentation initiation seems to depend entirely on the total number of treatments, not their frequency. However, treatment periods of more than 12 weeks may be necessary to obtain a satisfactory clinical repigmentation, particularly when vitiligo lesions are treated only 1 x or 2 x compared with 3 x weekly.

Adolescent↗

PubMed2005

Evaluation of the profile of thrombin generation during the process of whole blood clotting as assessed by thrombelastography.

The objective of this study was to evaluate the possibility of linking the tracing of whole blood clotting in a thrombelastograph (TEG) hemostasis system with the generation of thrombin assessed by thrombin/antithrombin complex (TAT). Citrated whole blood containing corn trypsin inhibitor from volunteers was clotted in the presence of CaCl2 and tissue factor. Clotting was monitored with the eight channels of a TEG system. At different time points, the whole blood TEG reaction cups were kept in a cold quenching solution, centrifuged, and the supernatants were kept at -80 degrees C until assayed for TAT by ELISA. The total thrombus generation (TTG) was calculated from the first derivative of the TEG waveform and was compared with thrombin generation measured by TAT. The two vector values--the TAT thrombin generation data and the corresponding TEG TTG--were analyzed using Pearson correlation coefficients (r) and linear, non-linear and natural log (ln) transformation of TAT values for least-squares goodness-of-fit curves. The best least-squares fit is an exponential curve. Linearizing using the ln of the TAT thrombin generation variable produces the same r (0.94) as of the exponential curve. The prediction equation is y = 8.0465 + 0.0005x (P < or = 0.0001), where y is the TAT thrombin generation variable in the ln transformation and x is the TEG TTG variable. The high magnitude of r and the high significance of the prediction equation demonstrate the high efficacy of the prediction of TAT thrombin generation by the use of TEG TTG.

Antithrombin III↗

PubMed2004

The role of alpha-synuclein gene multiplications in early-onset Parkinson's disease and dementia with Lewy bodies.

BACKGROUND: A triplication of the alpha-synuclein gene was found to cause autosomal dominant Lewy body disease in two distinct families. METHOD: We searched for alterations of alpha-synuclein gene dosage and analysed the entire coding region for point mutations in 54 dementia with Lewy body disease (DLB) and in 103 young onset Parkinson's disease (PD) patients from Central Europe. RESULTS: We could not detect any quantitative alterations in the gene dosage of alpha-synuclein. Mutational screening of the entire coding region of alpha-synuclein revealed only one silent mutation V3V (adenine9guanine) in one case. CONCLUSIONS: Thus, this phenomenon appears not to be a major cause in the pathogenesis of sporadic DLB and young onset PD in this European population.

Adult↗

PubMed2004

Genetics of osteochondral disease and its relationship with meat quality and quantity, growth, and feed conversion traits in pigs.

The main objective of this research was to estimate heritabilities of seven osteochondrosis (OC) lesions in station-tested pigs and their genetic and phenotypic correlations with four meat quality (MQ) traits, the percentage of premium cuts (PPC), daily weight gain (DWG), and feed conversion ratio (FCR). Observed OC lesions were on the head of humerus (HK), condylus medialis humeri (CMH), condylus lateralis humeri (CLH), radius and ulna proximal (RUP), distal epiphyseal cartilage of ulna (DEU), head of femur (FK), and condylus medialis femoris (CMF). Meat quality traits were i.m. fat (IMF), muscle pH at 1 h after slaughter (pH1), muscle pH at 30 h after slaughter (pH30), and light reflectance on muscle (H30). The data set comprised 2,710 animals, of which 1,291 animals had OC records. All traits were analyzed by multiple-trait linear mixed model, with the animal's genetic and common litter effects as random. Fixed effects in the model varied between traits. Each OC lesion was further analyzed by a univariate generalized linear mixed model or, equivalently, "threshold models," assuming logistic, probit (normal), and Poisson distributions of the underlying "liability" to the disease. For OC lesions, estimates of heritability were low on the original "incidence" scale (0.06 for HK to 0.16 for CLH) and moderate to high on the liability scale (0.08 to 0.42). Genetic correlations (r(g)) between OC lesions and most MQ traits and PPC were generally unfavorable. Significant r(g) were -0.44 for DWG-CMH, 0.31 for DWG-CMF, 0.40 for FCR-HK, 0.21 for PPC-CLH, 0.32 for PPC-RUP, 0.30 for PPC-CMF, -0.54 for pH1-CLH, 0.47 for pH1-DEU, -0.34 for pH30-CMH, 0.58 for pH30-DEU, -0.50 for H30-HK, -0.31 for H30-DEU, and 0.31 for H30-CMF. Genetic susceptibilities to some OC lesions within the front leg were positively related to each other (r(g) range = 0.57 to 0.69), but r(g) between front and hind leg OC lesions were mostly negative (range = -0.21 to -0.40). Estimated h2 was 0.60 for PPC, and ranged from 0.12 to 0.66 for MQ traits, 0.28 for DWG, and 0.42 for FCR. Genetic correlations among meat quality and quantity traits ranged from -0.66 to 0.37. This is the first study to report genetic and phenotypic correlations between OC lesions and several meat quality and quantity traits in pigs. These findings will be useful to pig industry, especially in designing breeding programs for robust pigs.

Aging↗

PubMed2003

Brain activation pattern during a verbal fluency test in healthy male and female volunteers: a functional magnetic resonance imaging study.

Sex differences in executive speech tasks, favoring women, have been noted in behavioral studies and functional imaging studies. In the present study ten female and ten male volunteers underwent functional magnetic resonance imaging in a conventional block design. All subjects were selected on the basis of high performance on the verbal fluency task. Regions of activation were detected after performance of a covert lexical verbal fluency task inside the scanner. Men and women who did not differ significantly in verbal fluency task performance showed a very similar pattern of brain activation. Our data argue against genuine between-sex differences in cerebral activation patterns during lexical verbal fluency activities when confounding factors like performance differences are excluded.

Adult↗

PubMed2003

Sex differences in brain activation pattern during a visuospatial cognitive task: a functional magnetic resonance imaging study in healthy volunteers.

Sex differences in mental rotation tasks, favoring men, have been noted in behavioral studies and functional imaging studies. In the present study ten female and ten male volunteers underwent functional magnetic resonance imaging in a conventional block design. Regions of activation were detected after performance of a mental rotation task inside the scanner. In contrast to previous studies, confounding factors such as performance differences between genders or high error rates were excluded. Men showed significantly stronger parietal activation, while women showed significantly greater right frontal activation. Our results point to gender specific differences in the neuropsychological processes involved in mental rotation tasks.

Brain↗

PubMed2003

L -dopa-induced adverse effects in PD and dopamine transporter gene polymorphism.

OBJECTIVE: To assess whether polymorphisms in the dopamine receptor genes and in the dopamine transporter gene (DAT ) are predictors of adverse effects of L -dopa. METHODS: A retrospective noninterventional study with 183 patients with PD was conducted. Nine polymorphisms of the dopamine D2 receptor (DRD2 ), two of the dopamine D3 receptor (DRD3 ), three of the dopamine D4 receptor (DRD4 ), and one variable number of tandem repeats (VNTR) of the DAT were studied. The entire coding and promoter regions of the DRD2 gene of 48 patients with early and severe appearance of adverse effects from L -dopa treatment and of eight never-afflicted patients were sequenced. RESULTS: The polymorphisms of DRD2, DRD3, and DRD4 were not associated with the risk to develop adverse effects of L -dopa. However, patients with psychosis or dyskinesia carried the nine copy allele 40-bp VNTR of the DAT more frequently than nonafflicted patients (60.0 vs 36.8%, p = 0.008; and 54.7 vs 32.9%, p = 0.006). Sequencing of the DRD2 gene revealed no new mutation, with the exception of one silent mutation in exon 6. CONCLUSIONS: Genetic variations of the DRD2, DRD3, and DRD4 do not influence the occurrence of L -dopa-induced adverse effects. However, the nine copy allele 40-bp VNTR of the DAT is a predictor for the occurrence of psychosis or dyskinesia in L -dopa-treated patients.

Aged↗

PubMed2002

[Psoriasis and hypogonadism in chronic blepharokeratoconjunctivitis. A case report].

BACKGROUND: Ocular symptoms occur in approximately 10% of patients with psoriasis vulgaris. PATIENT: We report the clinical course of a 35-year-old male patient with obstructive meibomian gland dysfunction, keratoconjunctivitis and reduced reflex secretion of both eyes. Psoriasis vulgaris and hypothalamic hypogonadism were also present. Genetic testing (cytogenetic and DNA analysis) was performed because of additional facial dysmorphia, brachydactylia and obesity. No chromosomal anomaly was found and no genetic syndrome has yet been diagnosed. The therapeutic regimen included preservative-free artificial tears, occlusion of the puncta and a systemic dose of doxycycline. Dermatological symptoms were treated topically and the hypogonadism was treated with intramuscular injections of testosterone. CONCLUSION: Lacrimal and meibomian glands are influenced by androgens. Therefore hormonal dysfunction can also have contributed to the blepharokeratoconjunctivitis in this patient.

Abnormalities, Multiple↗

PubMed2001

Trypanosoma brucei CTP synthetase: a target for the treatment of African sleeping sickness.

The drugs in clinical use against African sleeping sickness are toxic, costly, or inefficient. We show that Trypanosoma brucei, which causes this disease, has very low levels of CTP, which are due to a limited capacity for de novo synthesis and the lack of salvage pathways. The CTP synthetase inhibitors 6-diazo-5-oxo-l-norleucine (DON) and alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (acivicin) reduced the parasite CTP levels even further and inhibited trypanosome proliferation in vitro and in T. brucei-infected mice. In mammalian cells, DON mainly inhibits de novo purine biosynthesis, a pathway lacking in trypanosomes. We could rescue DON-treated human and mouse fibroblasts by the addition of the purine base hypoxanthine to the growth medium. For treatment of sleeping sickness, we propose the use of CTP synthetase inhibitors alone or in combination with appropriate nucleosides or bases.

Adenosine Triphosphate↗