The effect of systematic exercise training on skeletal muscle strength in a patient with advanced inclusion body myositis: A case study.

Inclusion body myositis (IBM) is an inflammatory and degenerative autoimmune disease that targets specific muscle groups, causing severe muscle weakness. Exercise training is often contraindicated in myopathies as it may aggravate muscle damage and inflammation. Although some reported positive outcomes in muscle strength of early diagnosed IBM patients undergoing resistance training, there remains uncertainty as to whether exercise could be beneficial and safe in advanced stage IBM. Thus the aims of this research were to evaluate the safety and response of 16-weeks supervised resistance training on the health and muscle performance of an elderly participant diagnosed with advanced stage IBM. It was shown that the training had no adverse effects on the health of the patient. Muscle strength measured at eight weeks and on completion of the intervention, remained the same as at baseline. In conclusion, the exercise programme was found to be safe and seemed to maintain muscle strength in a patient with advanced stage IBM.

Planctopirus ephydatiae, a novel Planctomycete isolated from a freshwater sponge.

The microbiome of freshwater sponges is rarely studied, and not a single novel bacterial species has been isolated and subsequently characterized from a freshwater sponge to date. A previous study showed that 14.4% of the microbiome from Ephydatia fluviatilis belong to the phylum Planctomycetes. Therefore, we sampled an Ephydatia sponge from a freshwater lake and employed enrichment techniques targeting bacteria from the phylum Planctomycetes. The obtained strain spb1T was subject to genomic and phenomic characterization and found to represent a novel planctomycetal species proposed as Planctopirus ephydatiae sp. nov. (DSM 106606 = CECT 9866). In the process of differentiating spb1T from its next relative Planctopirus limnophila DSM 3776T, we identified and characterized the first phage - Planctopirus phage vB_PlimS_J1 - infecting planctomycetes that was only mentioned anecdotally before. Interestingly, classical chemotaxonomic methods would have failed to distinguish Planctopirus ephydatiae strain spb1T from Planctopirus limnophila DSM 3776T. Our findings demonstrate and underpin the need for whole genome-based taxonomy to detect and differentiate planctomycetal species.

Greater performance impairment of black runners than white runners when running in hypoxia.

This study aimed to compare the response of performance-matched black and white runners during maximal and sub-maximal running in normoxic and hypoxic conditions. 14 well-trained runners (8 black, 6 white) performed 2 incremental maximal exercise tests and 2 fatigue resistance tests at 21% O2 (normoxia) or 14% O2 (hypoxia). Respiratory parameters, heart rate (HR), lactate concentration ([La(-)]) as well as arterial saturation (SpO2) were measured. Enzyme activities and myosin heavy chain content (MHC) were also measured. White runners reached a significantly greater peak treadmill speed and a higher HRmax than black runners in hypoxia (p<0.05). Additionally, White runners achieved a greater time to fatigue than black runners (p<0.05), with black runners displaying a greater decline in performance in hypoxia compared to normoxia (20.3% vs. 13.4%, black vs. white, respectively). However, black runners presented lower [La(-)] and higher SpO2 than white runners in hypoxia (p<0.05). Black runners had a higher proportion of MHC IIa and higher lactate dehydrogenase activity (p<0.05). The greater performance impairment observed in black runners in hypoxia suggests a greater performance sensitivity to this condition, despite the maintenance of physiological variables such as SpO2 and [La (-) ] within a smaller range than white runners.

Specific muscle adaptations in type II fibers after high-intensity interval training of well-trained runners.

High-intensity interval training (HIIT) forms an important component of endurance athletes' training, but little is known on intramuscular metabolic and fiber type adaptations. This study investigated physiological and skeletal muscle adaptations in endurance runners subjected to 6 weeks HIIT. Eighteen well-trained endurance athletes were subjected to 6 weeks HIIT. Maximal and submaximal exercise tests and muscle biopsies were performed before and after training. Results indicated that peak treadmill speed (PTS) increased (21.0 ± 0.8 vs 22.1 ± 1.2 km/h, P<0.001) and plasma lactate decreased at 64% and 80% PTS (P<0.05) after HIIT. Cross-sectional area of type II fibers tended to have decreased (P=0.06). No changes were observed in maximal oxygen consumption, muscle fiber type, capillary supply, citrate synthase and 3-hydroxyacetyl CoA dehydrogenase activities. Lactate dehydrogenase (LDH) activity increased in homogenate (P<0.05) and type IIa fiber pools (9.3%, P<0.05). The change in the latter correlated with an absolute interval training speed (r=0.65; P<0.05). In conclusion, HIIT in trained endurance runners causes no adaptations in muscle oxidative capacity but increased LDH activity, especially in type IIa fibers and in relation to absolute HIIT speed.

Vertical harvesting in hair transplantation.

BACKGROUND: There are several methods for harvesting from donor area, including punch graft, multiple bladed knife, or single bladed knife excision followed by excision of an ellipse. Vertical harvesting is excellent for avoiding follicular transections because of complete visualization of the angle of the hair exiting the scalp. Also, the donor area is easier to visualize because of rock-hard tumescence achieved during the totality of procedure. Only an experienced surgeon using a multiple bladed knife would have fewer follicular transections. OBJECTIVE: Optimal yield of the donor area: ie, minimal transection, thus less hair follicle transection. METHOD: Vertical harvesting of slivers of hair measuring 0.75-1.85 cm in height, and 3-4 millimeters in width using #10 solitary bladed knife and Optivisor (as magnification). RESULT: In our opinion, there is less transection of the follicular bulbs leading to an increase in yield. CONCLUSION: Patient comfort is maximized because the patient lies on one side. Another advantage is the reduced role of the technician, therefore requiring fewer technicians.

Similar pattern of thymic-dependent T-cell reconstitution in infants with severe combined immunodeficiency after human leukocyte antigen (HLA)-identical and HLA-nonidentical stem cell transplantation.

Donor T cells after stem cell transplantation reconstitute by 2 different pathways: by expansion from grafted, mature T cells and by intrathymic maturation from progenitor cells. This study characterized thymic-dependent reconstitution of CD4(+) T cells following different transplant modalities in patients with severe combined immunodeficiency (SCID). Three groups of patients were studied: one group after transplantation from human leukocyte antigen (HLA)-identical siblings with unmanipulated grafts without conditioning, a second group after transplantation from HLA-nonidentical parents with T-cell-depleted grafts without preconditioning, and a third group with prior conditioning. Reconstitution of the T-cell compartment was monitored by determining the expression of CD45 isoforms by developing CD4(+) cells in the peripheral blood and in discriminating expanded (CD45RO(+)) and newly generated (CD45RA(+)) T cells. Concomitantly, changes in the size of the thymus were evaluated sequentially by ultrasonography. Reconstitution of CD4(+)CD45RA(+) cells was delayed in all patients for several months, including patients after HLA-identical transplantation, and was always paralleled by normalization of the size of the thymus. No engraftment of donor progenitor cells was observed, as studied in one patient transplanted without conditioning. CD4(+)CD45RO(+) cells were detected early after transplantation only in patients given unmanipulated grafts. The study showed that thymic-dependent T-cell maturation in these patients with SCID runs an autonomous course, independent of graft manipulation, of major HLA disparities, and of whether conditioning is used or not. In addition, thymic maturation may not require engraftment of donor-derived CD34(+) cells in the marrow. (Blood. 2000;96:4344-4349)

Diamino benzo[b]thiophene derivatives as a novel class of active site directed thrombin inhibitors. Part 6: further focus on the contracted C4'-side chain analogues.

Novel benzo[b]thiophene diamine thrombin inhibitors were investigated, focusing on a contracted C4'-side chain series. SAR studies identified compounds with either a pyrrolidino or morpholino group as potent, active site directed thrombin inhibitors when the amino group was connected to the C3-phenyl ring with a methylene linker at the C4' position of the phenyl ring.

Diamino benzo[b]thiophene derivatives as a novel class of active site directed thrombin inhibitors. 5. Potency, efficacy, and pharmacokinetic properties of modified C-3 side chain derivatives.

A systematic investigation of the structure-activity relationships of the C-3 side chain of the screening hit 1a led to the identification of the potent thrombin inhibitors 23c, 28c, and 31c. Their activities (1240, 903, and 1271 x 10(6) L/mol, respectively) represent 2200- and 2900-fold increases in potency over the starting lead 1a. This activity enhancement was accomplished with an increase of thrombin selectivity. The in vitro anticoagulant profiles of derivatives 28c and 31c were determined, and they compare favorably with the clinical agent H-R-1-[4aS, 8aS]perhydroisoquinolyl-prolyl-arginyl aldehyde (D-Piq-Pro-Arg-H; 32). The more potent members of this series have been studied in an arterial/venous shunt (AV shunt) model of thrombosis and were found to be efficacious in reducing clot formation. However, their efficacy is currently limited by their rapid and extensive distribution following administration.

Effects of postnatal estradiol and progesterone replacement in extremely preterm infants.

The fetus is supplied from the placenta with estradiol (E2) and progesterone (P) in increasing amounts during gestation. After delivery of a premature infant, placental supply is disrupted, resulting in a rapid decrease in E2 and P. Replacement of these placental hormones may restore intrauterine conditions and may be beneficial for bone mineral accretion, clinical course, and outcome. Thirty female infants with a median gestational age of 26.6 weeks (between 24.1-28.7) and a birth weight of 675 g (370-990) were randomized to receive E2 and P replacement, aiming to maintain plasma levels equaling the intrauterine levels, or no replacement. The E2 and P replacement was started iv and was followed by transepidermal administration for a total duration of 6 weeks. Repeated measurements included plasma levels of E2, P, FSH, and LH; uterine volume; calcium and phosphorus in spot urine specimens; and bone mineral accretion by single photon absorption densitometry. Further, the incidence of chronic lung disease and various clinical outcome data were recorded. The plasma levels of E2 and P were within the intrauterine range with median replacements of 2.30 mg/kg x day E2 (1.13-6.23) and 21.20 mg/kg x day P (11.23-27.36), iv. Three- and 6-fold higher doses of E2 and P were needed via the transepidermal route. The uterine volumes increased, and FSH and LH as indicators for biological effectiveness were significantly lowered with replacement. The bone mineral accretion rates tended to be higher, and the incidence of chronic lung disease tended to be lower (0% vs. 29%; P = 0.097). E2 and P replacement via iv and transepidermal routes is capable of maintaining plasma levels as high as those in utero with biological effectiveness. Trends toward improved postnatal bone mineral accretion and less chronic lung disease were found with the hormone replacement. Further and more extensive studies are warranted to address the role of this new approach in the care of extremely premature infants.

Dibasic benzo[B]thiophene derivatives as a novel class of active site directed thrombin inhibitors: 4. SAR studies on the conformationally restricted C3-side chain of hydroxybenzo[B]thiophenes.

A novel series of benzo[b]thiophene diamine thrombin inhibitors with a conformationally restricted C3-side chain 3 was investigated. The constrained C3-side chain by a cyclohexyl ring contributed to not only an additive but also a synergistic effect on the thrombin inhibitory activity. The SAR studies resulted in the discovery of a potent thrombin inhibitor 27 that was over 750-fold more potent than the initial lead compound 1.

Dibasic benzo[b]thiophene derivatives as a novel class of active site directed thrombin inhibitors: 2. Sidechain optimization and demonstration of in vivo efficacy.

Potent, subnanomolar thrombin inhibitors 4, 5, and 6 are developed through side chain optimization of novel, benzo[b]thiophene-based small organic entities 2 and 3 and through SAR additivity studies of the new structural elements identified. X-ray crystallographic studies of 4b-thrombin complex revealed a hydrophobic and an electrostatic interaction of these new elements with thrombin at the S2 and S3 binding sites. In vitro and in vivo pharmacological studies showed that 4, 5, and 6 are potent anticoagulants in human plasma with demonstrated antithrombotic efficacy in a rat model of thrombosis.

Development of dual-acting agents for thromboxane receptor antagonism and thromboxane synthase inhibition. 2. Design, synthesis, and evaluation of a novel series of phenyl oxazole derivatives.

Synthesis and initial in vitro evaluation of a novel series of phenyl oxazole derivatives are described. An SAR study of the novel dual-acting TRA/TSI agent has revealed that the lipophilicity of the oxazole amide substituents greatly influences the TRA activity but not the TSI. The chain length of the alkenoic acid side chain affects both TRA and TSI. The optimal chain length for the combined activities was found to be n = 4 (heptenoic acid).

Development of dual-acting agents for thromboxane receptor antagonism and thromboxane synthase inhibition. 3. Synthesis and biological activities of oxazolecarboxamide-substituted omega-phenyl-omega-(3-pyridyl)alkenoic acid derivatives and related compounds.

A novel series of oxazolecarboxamide-substituted omega-phenyl-omega-(3-pyridyl)alkenoic acid derivatives was discovered as potent dual-acting agents to block the TXA2 receptor and to inhibit the thromboxane synthase (TRA/TSI). Synthesis, structure-activity relationship (SAR), and in vitro and in vivo pharmacology of this series of compounds are described. Modification of the series revolved around the oxazole moiety to increase the hydrophilicity of the compounds and to correlate the biological activity with lipophilicity of the compounds. The most potent in the series was (E)-7-[4-[4-[[(4-cyclohexylbutyl)amino]carbonyl]-2-oxazolyl] phenyl]-7 -(3-pyridyl)hept-6-enoic acid (14) with Kd = 9.9 +/- 0.4 nM for the thromboxane receptor antagonism and IC50 = 55.0 +/- 17.9 nM for thromboxane synthase inhibition. The compound 14 was a selective TRA/TSI which exhibited desirable characteristics for oral activity, "shunt" effect to elevate PGI2 level, and absence of agonist activity.

[Histomorphology of BCG infections in patients with severe combined immunodeficiency]. / Histomorphologie der BCG-Infektion bei angeborenem schwerem kombinierten Immundefekt.

Most inborn immunodeficiency syndromes clinically become overt by complicating infections, e.g. by BCG-infection after BCG-vaccination. The diagnostic approach often is hampered by an atypical histomorphological picture of the infection caused by the underlying immune defect. We examined biopsies of different organs in 18 infants with severe combined immunodeficiency syndrome and BCG-infection. A number of unusual histomorphological patterns of BCG-infection were found not yet published previously. There was a correlation between histomorphological features and immunological data or clinical course in most cases.