Peripheral and Autonomic Neuropathy Status of Young Patients With Type 1 Diabetes Mellitus at the Time of Transition From Pediatric Care to Adult-Oriented Diabetes Care.

Introduction: The prevalence of neuropathic lesions in young patients with type 1 diabetes mellitus (T1DM) at the time of transition from pediatric care to adult-oriented diabetes care is poorly studied. A comparative study with healthy volunteers to assess the possible neuropathic condition of this special population and to identify the potential early screening needs has not been performed yet. The results may provide important feedback to pediatric diabetes care and a remarkable baseline reference point for further follow up in adult diabetes care. Patients and Methods: Twenty-nine young patients with T1DM [age: 22.4 ± 2.9 years; HbA1c: 8.5 ± 2.1%, diabetes duration: 12.2 ± 5.8 years; (mean ± SD)] and 30 healthy volunteers (age: 21.5 ± 1.6 years; HbA1c: 5.3 ± 0.3%) were involved in the study. Autonomic function was assessed by standard cardiovascular reflex tests. Complex peripheral neuropathic testing was performed by Neurometer®, Neuropad®-test, Tiptherm®, Monofilament®, and Rydel-Seiffer tuning fork tests. Results: T1DM patients had significantly higher diastolic blood pressure than controls (80 ± 9 vs. 74 ± 8 mmHg, p < 0.01), but there was no significant difference in systolic blood pressure (127 ± 26 vs. 121 ± 13 mmHg). Cardiovascular reflex tests had not revealed any significant differences between the T1DM patients and controls. No significant differences with Neurometer®, Neuropad®-test, and Monofilament® were detected between the two groups. The vibrational sensing on the radius on both sides was significantly impaired in the T1DM group compared to the controls with Rydel-Seiffer tuning fork test (right: 7.5 ± 1.0 vs. 7.9 ± 0.3; left: 7.5 ± 0.9 vs. 7.9 ± 0.3, p < 0.05). The Tiptherm®-test also identified a significant impairment in T1DM patients (11 sensing failures vs. 1, p < 0.001). In addition, the neuropathic complaints were significantly more frequently present in the T1DM patient group than in the controls (9 vs. 0, p < 0.01). Conclusion: In this young T1DM population, cardiovascular autonomic neuropathy and cardiac morphological alterations could not be found. However, Rydel-Seiffer tuning fork and Tiptherm®-tests revealed peripheral sensory neurological impairments in young T1DM patients at the time of their transition to adult diabetes care.

Protonated rhodosemiquinone at the Q(B) binding site of the M265IT mutant reaction center of photosynthetic bacterium Rhodobacter sphaeroides.

The second electron transfer from primary ubiquinone Q(A) to secondary ubiquinone Q(B) in the reaction center (RC) from Rhodobacter sphaeroides involves a protonated Q(B)(-) intermediate state whose low pK(a) makes direct observation impossible. Here, we replaced the native ubiquinone with low-potential rhodoquinone at the Q(B) binding site of the M265IT mutant RC. Because the in situ midpoint redox potential of Q(A) of this mutant was lowered approximately the same extent (≈100 mV) as that of Q(B) upon exchange of ubiquinone with low-potential rhodoquinone, the inter-quinone (Q(A) → Q(B)) electron transfer became energetically favorable. After subsequent saturating flash excitations, a period of two damped oscillations of the protonated rhodosemiquinone was observed. The Q(B)H(•) was identified by (1) the characteristic band at 420 nm of the absorption spectrum after the second flash and (2) weaker damping of the oscillation at 420 nm (due to the neutral form) than at 460 nm (attributed to the anionic form). The appearance of the neutral semiquinone was restricted to the acidic pH range, indicating a functional pK(a) of <5.5, slightly higher than that of the native ubisemiquinone (pK(a) < 4.5) at pH 7. The analysis of the pH and temperature dependencies of the rates of the second electron transfer supports the concept of the pH-dependent pK(a) of the semiquinone at the Q(B) binding site. The local electrostatic potential is severely modified by the strongly interacting neighboring acidic cluster, and the pK(a) of the semiquinone is in the middle of the pH range of the complex titration. The kinetic and thermodynamic data are discussed according to the proton-activated electron transfer mechanism combined with the pH-dependent functional pK(a) of the semiquinone at the Q(B) site of the RC.

The rate of second electron transfer to QB(-) in bacterial reaction center of impaired proton delivery shows hydrogen-isotope effect.

The 2nd electron transfer in reaction center of photosynthetic bacterium Rhodobacter sphaeroides is a two step process in which protonation of QB(-) precedes interquinone electron transfer. The thermal activation and pH dependence of the overall rate constants of different RC variants were measured and compared in solvents of water (H2O) and heavy water (D2O). The electron transfer variants where the electron transfer is rate limiting (wild type and M17DN, L210DN and H173EQ mutants) do not show solvent isotope effect and the significant decrease of the rate constant of the second electron transfer in these mutants is due to lowering the operational pKa of QB(-)/QBH: 4.5 (native), 3.9 (L210DN), 3.7 (M17DN) and 3.1 (H173EQ) at pH7. On the other hand, the proton transfer variants where the proton transfer is rate limiting demonstrate solvent isotope effect of pH-independent moderate magnitude (2.11±0.26 (WT+Ni(2+)), 2.16±0.35 (WT+Cd(2+)) and 2.34±0.44 (L210DN/M17DN)) or pH-dependent large magnitude (5.7 at pH4 (L213DN)). Upon deuteration, the free energy and the enthalpy of activation increase in all proton transfer variants by about 1 kcal/mol and the entropy of activation becomes negligible in L210DN/M17DN mutant. The results are interpreted as manifestation of equilibrium and kinetic solvent isotope effects and the structural, energetic and kinetic possibility of alternate proton delivery pathways are discussed.

Adrenal haemorrhage in term neonates: a retrospective study from the period 2001-2013.

OBJECTIVE: To assess the incidence, risk factors and clinical presentations of neonatal adrenal haemorrhage (NAH) in uncomplicated, singleton and term deliveries. METHODS: A retrospective analysis of 26,416 term neonates delivered between 2001 and 2013, and screened with abdominal ultrasonography. RESULTS: Of the 26,416 neonates, 74 (0.28%) displayed NAH; the male/female ratio was 1.55:1. Vaginal delivery was significantly more frequent than caesarean section among them (71 versus 3; 95.9% versus 4.1%). Unilateral bleeding occurred on the right side in 36 (48.7%), and on the left in 34 (45.9%), without a significant difference; bilateral haematomas were found in four cases (5.4%). The most common risk factors were macrosomia (16, 21.6%) and fetal acidaemia (23, 31%), while four (5.4%) neonates exhibited pathological acidaemia. Clinical presentations included jaundice in 37 (50%), anaemia in six (8.1%) and an adrenal insufficiency in only one (1.3%) case. In three cases, neuroblastoma was diagnosed. CONCLUSIONS: Vaginal delivery, macrosomia and fetal acidaemia are the most important risk factors for NAH. The adrenal glands on both sides were similarly involved. In the healthy neonates with NAH, the clinical presentations were mild, with spontaneous regression. Differentiation of NAH from tumours is of considerable importance.