Fully vs. partially integrated services for TB-HIV in Myanmar: a health services review and a cohort study.

In Myanmar, integrated services for tuberculosis (TB) and human immunodeficiency virus (HIV) are operated either fully (as one single unit) or partially (each vertical programme provides both services). To review the fully and partially integrated services for TB-HIV and to assess their TB treatment outcomes. We analysed the compiled service database and conducted a cohort study on newly registered TB-HIV patients in 12 townships in Myanmar. No significant association between region/state and types of integration was detected. Townships with partially integrated services had a significantly larger population size, higher proportion of urban population as well as higher TB and TB-HIV case notification rates; however, the cartridge-based Xpert® MTB/RIF assay was used less frequently than in townships with fully integrated services. Treatment completion rate and unfavourable outcomes were not significantly different between the two models, although fully integrated services reported a higher cure rate. These mixed results suggest that during expansion of fully integrated services, the progress of treatment outcomes should be monitored carefully. .

High prevalence and incidence of tuberculosis in people living with the HIV in Mandalay, Myanmar, 2011-2017.

SETTING: Two human immunodeficiency virus (HIV) clinics providing antiretroviral therapy (ART), Mandalay, Myanmar. OBJECTIVE: To assess prevalent TB at enrolment, incident TB during follow-up and associated risk factors in adult people living with HIV (PLHIV) between 2011 and 2017. DESIGN: Cohort study using secondary data. RESULTS: Of 11 777 PLHIV, 2911 (25%) had prevalent TB at or within 6 weeks of enrolment. Independent risk factors for prevalent TB were being male or single/widowed, daily alcohol consumption, CD4 count 200 cells/µl and anaemia. During 6 years follow-up in 8866 PLHIV with no prevalent TB, the rate of new TB was 2.9 per 100 person-years (95%CI 2.6-3.1). Cumulative TB incidence was 9.6%, with 370 (72%) of 517 new TB cases occurring in the first year. Independent risk factors for incident TB were being male and anaemia. Incident TB was highest in the first year of ART, in PLHIV with CD4 counts 200 cells/µl and those not receiving isoniazid preventive therapy (IPT). Incident TB declined with time on ART and rising CD4 counts. CONCLUSION: Prevalent and incident TB were high in PLHIV in the Mandalay clinics. Consideration should be given to earlier TB diagnosis using more sensitive diagnostic tools, effective ART and scaling up IPT.

[Pretective action of peptide pro-gly-pro on electrophysiological characteristics of cultured hippocampal neurones during excitotoxic damage].

Electrophysiological characteristics of hippocampal neurones cultured with Pro-Gly-Pro peptide were studied using glutamate excitotoxisity model (excitotoxic damage was induced by 100 mkM glutamate application during 5 min). It was found that negative changes in neurones cultured with 10 mcM Pro-Gly-Pro were less prominent if compared with control ones. Culturing with the peptide significantly affected the following parameters: resting potential (-55 +/- 4 mV in control; -29 +/- 6 MV after glutamate application; -38 +/- 5 MV cultured after glutamate application), action potential amplitude (91 +/- 4; 65 +/- 5; 84 +/- 5 mV), duration (4,3 +/- 0,4; 9,5 +/- 1,6; 5,2 +/- 0,7 ms), depolarization (56 [38, 84]; 27 [21, 35]; 46 [28, 62] MV/Ms) and repolarization (-29 [-38, -27]; -20 [-21, -18]; -29 [-33, -22] M(V)/MS) rates. The data obtained suggest that PGP exhibit its neuroprotective properties on a level of basic electrophysiological characteristics, appropriate cellular mechanisms require further investigations.

[Characteristics of quantal release of glutamate and GABA in synapses between retinal ganglion cells and superior colliculus neurons in coculture].

We investigated features of quantal release of glutamate and GABA in synapses between retinal ganglion cells (RGC) and superior colliculus (SC) neurons in coculture using dual patch-clamp technique. The main quantal characteristics of neurotransmitters release were defined on the basic of quantal analysis. Number of released quanta distributions for both neurotransmitters were corresponded to the binomial law. It was shown that evoked postsynaptic currents (PSC) in SC neurons as response to generation of action potential (AP) in RGC were mediated by simultaneous release at least from 2 to 14 quanta of glutamate and 2 quanta of GABA. Thereby high efficacy of excitatory and inhibitory signals transmission is guaranteed in retinocollicular projections. It is supposed that multiquantal character of the neurotransmitters release can be related to simultaneous involvement of several closely adjacent excited terminals, each of which possesses one active zone, or by one terminal with several.

[Changes in the kinetics of calcium signals in response to high frequency stimulation in the cultured hippocampal neurons].

Dynamic changes in the intracellular free Ca2+ concentration ([Ca2+]i) were studied in hippocampal cultured neurons using fluorescent Ca(2+)-indicator dye Indo-1 and somatic whole-cell recordings. During the tetanus stimulation Ca(2+)-transient increased their amplitude up to a steady-state level during repetitive stimulation. We identified two groups of neurons based on Ca-signal dynamics after the end of stimulation: the first group (n = 24) with the monoexponential decay of [Ca2+]i direct after the end of the tetanus; the second group (n = 32) with the monoexponential delayed [Ca2+]i decay after the end of the tetanus, the duration of delay varied from 1 to 27 s and depended on duration and frequency of stimulation. Peak amplitudes of Ca(2+)-transients were statistically different between the first (1820 +/- 195 nM, n = 24) and the second (2618 +/- 165 nM, n = 23) groups. A linear dependence between decay time constant and frequency of stimulation was found for the second group of neurons only. In all cases when the delayed decay was observed the decay time constant changed reliably after emergence of delayed decay; the average rise made up 41 +/- 8%. We suggest dynamic changes and essential rise in the intracellular free Ca2+ concentration arise from the presence of intracellular low-affinity buffer. This statement is to be further tested using pharmacological approach.

[Electrical properties of retinal ganglion cells of rats with streptozotocine-induced diabetes].

On isolated retinal preparation from STZ-induced diabetic rats in whole-cell configuration the basic electrical properties of retinal ganglion cells (RGC) were studied. It was shown that on 8th week after STZ maximal depolarization-induced firing frequency is reduced and decay time constant of high-frequency stimulation-induced calcium signals is increased as compared to controls. The data obtained suggest functional changes in RGC of STZ-induced diabetic rats, possible mechanisms of such changes are discussed.

[Pre- and postsynaptic expression mechanisms of long-term depression in rats glutamatergic primary afferent synapses on dorsal horn spinal cord neurons in co-culture].

In co-culture of dorsal root ganglion (DRG) and dorsal horn (DH) neurons we studied the long-term depression (LTD) caused by 5 sec(-1) low-frequency stimulation (LFS) of DRG neurons. Dual whole-cell patch clamp recording in the pairs of DRG and DH neurons was used. The monosynaptic AMPA-receptor mediated eEPSC initiated in DH neurons by LFS of DRG neurons were analyzed. LFS with durations from 60 to 360 sec affected the LTD magnitude and involved the different LTD expression mechanisms. The amplitude and variability of miniature EPSC were not changed during LTD. LFS during 60 sec did not alter the eEPSC amplitudes, but significantly increased the coefficient of variation (CV; 56.8% +/- 11.5%, n = 5; P < 0.002) and the paired-pulse ratio (PPR; 37.8% +/- 11.4%, n = 5; P < 0.05), and decreased the release probability (p; 21.9% +/- 5.6%, n = 5; P < 0.05) calculated using binomial analysis. LFS for 120 sec led to LTD (eEPSC decreased to 14% +/- 3.3%, n = 13; P < 0.005); no changes in CV, PPR and p were found. LFS for 160, 200, 240 and 360 sec induced robust LTD: eEPSC decreased to 37.3 +/- 4.3 (n = 9); 48.1 +/- 3.5 (n = 7); 58.3 +/- 2.5 (n = 8) and 57.3% +/- 2.8% (n = 8), respectively; P < 0.001. LTD induced by such LFS durations was not accompanied by significant changing in PPR and p, but showed an increase in CV: 24.4 +/- 8.6 (n = 6); 35.1 +/- 11.2 (n = 6); 37.7 +/- 12.8 (n = 7), and 38.1% +/- 9.3% (n = 8), respectively. LTD magnitude was correlated with the enhancement in CV value at different LFS duration (r = 0.96). Our data suggest that the different mechanisms could be involved in LTD expression according to duration of LFS. Thus, 60 sec LFS induces presynaptic changes, but no change in eEPSC, whereas LTD elicited by 120 and 160 sec LFS affected the postsynaptic site. LTD initiated by longer LFS (200 - 360 sec) probably was caused by a silencing of functional synapses without changes in glutamate release probability.

[Calcium signaling induced by tonic firing in the rat eye retinal ganglion cells].

On rat retinal preparation in whole-cell mode retinal ganglion cells (RGC) tonic firing induced calcium signals were recorded and their modulation by Kv3 potassium channels was studied. RGC depolarization with 500 ms current steps caused tonic action potentials (AP) generation and development of calcium signals which amplitude depended quite linearly on mean AP frequency with mean slope 1.4 +/- 0.2 s x nmol/l (n = 5). The calcium signals mean tau of decay value was 6.8 +/- 1.4 s (n = 5). After application of tetraethylammoniun (500 MM), which in such concentration blocks Kv3.1/Kv3.2 potassium channels, a decrease in firing frequency, an increase of AP width and a decrease of afterhyperpolarization amplitude were observed. In the presence of the blocker the calcium signal amplitude vs mean AP frequency dependency slope mean value increased to 2.1 +/- 0.3 s.nmol/l. The calcium signals tan of decay not changed significantly, the mean value was 8.9 +/- 1.6 s (n = 5). Thus, voltage-dependent Kv3.1/Kv3.2 potassium channels, which play a key role in tonic firing pattern generation in RGC, also modulate appropriate calcium signals and prevent the cells from significant intracellular calcium increasing and its possible cytotoxic action.

[Modern biotechnologies in estimation of genetic diversity of Ukrainian varieties of hop (Humulus lupulus L.)].

Genetic variety estimation of hop gene pool using DNA-typing of highly polymorphic microsatellite loci and optimization of introduction to the culture of in vitro conditions is the important stage of national varieties resources forming, basis of modern nursery and protect mean of varieties property, and also it is necessary for development of molecular methods of selection of planting-stocks free from pathogens.

[Characteristics of sensory neurotransmission in co-culture of neurons from the dorsal root ganglion and dorsal horn spinal cord in rats].

We examined properties of chemical neurotransmission at the level of primary afferent inputs into spinal cord with the new easy-to-use in vitro model of contiguously-cultivated dissociated both the dorsal root ganglion neurons (DRG) and the dorsal horn spinal cord neurons (DHSC) from newborn rats. The results of our studies showed the presence of excitatory and inhibitory DRG neurons synapses on the cells of DHSC. The excitatory afferent signaling in such synapses was mediated by presynaptic release of glutamate and a following activation of both NMDA- and non-NMDA-receptor subclasses. In these cases the activation of non-NMDA-receptors makes a main contribution to realization of excitatory postsynaptic effects. Either glycine- or GABA-ergic DRG neurons were involved in transmission of inhibitory signals to the DHSC neurons. However, in vast majority of examined neuronal pairs the inhibitory synaptic transmission was mediated by presynaptic release of glycine. As distinct from the previous similar methods, an in vitro model of co-culture of both the DRG and the DHSC neurons proposed here allows to use comprehensively modem technical approaches for examination of the transmission of somatosensory information from the periphery to the CNS. The described model could be acceptable for detailed investigation of specific properties of primary afferent synapses.

[Nonuniform distribution and contribution of the P- and P/Q-type calcium channels to short-term inhibitory synaptic transmission in cultured hippocampal neurons].

In the present study, we investigated the sensitivity of GABAergic short-term plasticity to the selective P- and P/Q-type calcium channels blocker omega-agatoxin-IVA. To block the P-type channels we used 30 nM of this toxin and 200 nM of the toxin was used to block the P/Q channel types. The evoked inhibitory postsynaptic currents (eIPSC) were studied using patch-clamp technique in whole-cell configuration in postsynaptic neuron and local extracellular stimulation of single presynaptic axon by rectangular pulse. The present data show that the contribution of P- and P/Q-types channels to GABAergic synaptic transmission in cultured hippocampal neurons are 30% and 45%, respectively. It was shown that the mediate contribution of the P- and P/Q-types channels to the amplitudes of eIPSC is different to every discovered neuron. It means that distribution of these channels is non-uniform. To study the short-term plasticity of inhibitory synaptic transmission, axons of presynaptic neurons were paired-pulse stimulated with the interpulse interval of 150 ms. Neurons demonstrated both the depression and facilitation. The application of 30 nM and 200 nM of the blocker decreased the depression and increased facilitation to 8% and 11%, respectively. In addition, we found that the mediate contribution of the P- and P/Q-types channels to realization of synaptic transmission after the second stimuli is 4% less compared to that after the first one. Therefore, blocking of both P- and P/Q-types calcium channels can change the efficiency of synaptic transmission. In this instance it facilitates realization of the transmission via decreased depression or increased facilitation. These results confirm that the P- and P/Q-types calcium channels are involved in regulation of the short-term inhibitory synaptic plasticity in cultured hippocampal neurons.

[Effect of 4-aminopyridine-sensitive potassium current on high frequency tonic firing of the rat retinal ganglion cells].

High frequency firing properties of the rat retinal ganglion cells and role of 4-AP-sensitive potassium current in firing generation were studied using whole cell patch-clamp techniques. Potassium channel blocker 4-AP (0,2 mM) reduced depolarization-evoked firing rate by 62% (from 50 +/- 5, n = 12 to 19 +/- 2 Hz, n = 7). Single action potential parameters were affected: half-width was increased by 133% (from 1,2 +/- 0,1, n = 12 to 2,8 +/- 0,3 ms, n = 7), decay slope was decreased by 63% (from 102 +/- 11, n = 12 to 38 +/- 7 mV/ms, n = 7) and afterhyperpolarization amplitude by 83% (from 18 +/- 2, n = 12 to 3 +/- 2 mV, n = 7). 4-AP application (0,2 mM) reduced potassium current amplitude of the retinal neurons. 4-AP-sensitive current was obtained by digital subtraction of current that was registered in the presence of the blocker from control current records (1,61 +/- 0,22 nA, n = 6). 4-AP-sensitive current was equal to 0,40 +/- 0,09 nA (n = 6). Thus, moderate (25%) reducing of potassium current amplitude leads to essential changes in firing properties of retinal neurons. 4-AP-sensitive residual current was similar to Kv3.1/Kv3.2 potassium currents that were described in literature previously. Moreover, we excluded the possibility of 4-AP influence on Kv1 channels by specific blocker alpha-dendrotoxin (100 nM) application. Such applications significantly affected neither firing frequency nor single action potential parameters. The data obtained suggest that 4-AP-sensitive current plays a key role in high frequency firing generation in the rat retinal ganglion cells. We assume that the 4-AP-sensitive current is mediated by Kv3.1/Kv3.2 conductance.

[The role of N-type high-voltage-activated calcium channels in plasticity regulation of inhibitory synaptic transmission in cultured hippocampal neurons].

Now it is clear that N-type Ca2+ channels contribute to synaptic transmission at many of CNS synapses. However, it is not known whether presynaptic N-type Ca2+ channels contribute to short-term synaptic plasticity (STP) mediated by GABA release at inhibitory synapses of cultured hippocampal neurons. We studied the sensitivity of GABAergic paired pulse depression (PPD) as a common form of STP to selective N-type high-voltage-activated Ca2+ channels blocker omega-conotoxin (omegaCgTx). Evoked inhibitory postsynaptic currents (eIPSCs) were studied using patch-clamp technique in whole-cell configuration in postsynaptic neuron and local exteracellular paired pulse stimulation of single presynaptic axon by rectangular pulse with 0.4 ms duration, the interpulse interval in pair was 150 ms. CgTx (200 nM; 1 microM) in a dose-dependent manner irreversibly reduced the amplitude of paired eIPSCs by 25-49% and decreased PPD by 11-22% compared with control. These results confirm that N-type Ca2+ channels are highly involved in inhibitory synaptic transmission and short-term synaptic plasticity in cultured hippocampal neurons.

[Synaptic responses and intraganglionic connections of rat superior cervical ganglia neurons].

The rat superior cervical ganglion (SCG) neurones demonstrate responses on the threshold stimulation of the cervical sympathetic nerve, extrinsic (ECN) and intrinsic (ICN) carotid nerves. Both antidromic and synaptic responses were evoked by antidromic stimulation of ECN and ICN. The synaptic responses of each neuron differ by great variability amplitudes of the excitatory postsynaptic potentials and the currents, the rise time and the time constant decay of the postsynaptic current. We hypothesize that this variability of the synaptic responces is associated with the spatial distribution of synapses on the dendritic tree and on the neuron soma that are innervated by the single axon.

[Voltage-activated potassium channels of the inhibitory interneurons of the hippocampus in culture].

Potassium channels make up the largest family of voltage-activated channels and play a key role in maintenance of cell excitability and in transmission of information within the nervous system. The aim of this work was to find out the specific subtypes of voltage-activated potassium channels peculiar to GABAergic interneurons of rat hippocampal culture. It was shown that total depolarization-evoked outward potassium current in any interneuron studied had the activation threshold about -50 mV. The specific Kv1 channels' blocker a-DTX influenced neither amplitude nor kinetics of total current, thus we excluded the participation of these channels in its forming. The transient A-current made up 9.4+/-1.3% of the amplitude of total current and had low sensitivity to 4-AP that was an evidence of the presence of Kv4 channels in hippocampal interneurons. The slow inactivating component of integral potassium current was relatively small and had the time constant of inactivation 3 +/- 0.15 s that is typical for delayed rectifier potassium channels of Kv2 and Kv3 subfamilies. The main contribution (83 +/- 1.7 % of total amplitude) to the integral current belonged to the non-inactivating current. Prolonged depolarization of any interneuron tested to -20 mV evoked a steady non-inactivating outward current with amplitude 100-400 pA and activation threshold about -60 mV. Retigabine shifted its I-V plot to more negative values and increased the amplitude at -20 mV by 66+/-14%. These facts can be evidence of the participation of KCNQ channels subfamily in the forming of non-inactivating current. But selective blockers of KCNQ channels linopirdine and XE991 had very small influence on steady-state outward current that means the current appears owing to activity of linopirdine-insensitive forms of KCNQ channels or channels of a different, unknown family.

[Electrophysiological properties of inhibitory neurones in cultured dissociated hippocampal cells]. / Elektrofiziolohichni vlastyvosti hal'mivnykh neironiv u dysotsiiovanii kul'turi klityn hipokampa.

Electrophysiological properties of inhibitory (GABAergic) neurones were studied in dissociated hippocampal culture using simultaneous whole cell recordings from pairs of monosynaptically coupled neurons. Reliable identification of GABAergic neuron was performed by presence of monosynaptic inhibitory currents at postsynaptic cell in response to action potentials at stimulated cell. It was shown that GABAergic neurons in hippocampal culture are divided in two groups by their firing characteristics: first type generates action potentials at high frequency in response to injection of current (duration 0.5 s)--fast-spiking neurons (FS), cells from second type has no ability for high-frequency action potential generation--regular spiking neurons (RS). These two groups were distinguished by kinetic characteristics of action potentials, adaptation characteristics during continuous generation of action potentials and inhibitory effect making on postsynaptic cell. Application of potassium channel blocker 4-AP to somas of FS neurons in concentration, which selectively inhibits Kv3 potassium channels evoked reversible changes in kinetic of action potentials, frequency and adaptation characteristics during continuous generation of action potentials. It was concluded that there is hight level of expression of Kv3 potassium channels in the first group of neurons.

Improved detection of Mycobacterium spp. using the Bactec MGIT 960 system.

Until 1987, the notification rate for mycobacterial infection was on the decline; however, it now appears to be increasing once more. The reason for this may be multifactoral and include improved reporting of diagnosed cases, increased infection of an ageing population, homelessness, immunosuppression (e.g. due to human immunodeficiency virus infection), and immigration of people from countries where tuberculosis is endemic. This rising incidence and the increasing importance of resistant organisms mean that rapid identification by the clinical microbiology laboratory is required, and this is where an automated detection system can be an advantage. Over a two-year period, 2743 clinical specimen were examined for Mycobacterium spp. using the Bactec MGIT 960, and 286 were positive. Time to detection ranged from three to 14 days (mean: 9.3 days), and M. tuberculosis was recovered from 214 (75.5%). Contamination rate was higher (8.6%) than with manual methods, however. On balance, the Bactec MGIT 960 system proved a valuable tool in the routine microbiology laboratory.

[Ionic currents responsible for activation of isolated retinal ganglion cells]. / Ionni strumy, shcho zabespechyiut' elektrychnu zbudlyvist' izol'ovanykh hanhlioznykh klityn sitkivky oka shchuriv.

Ionic currents responsible for excitability of retinal ganglion cells (RGC) freshly isolated from eyes of adult rats were studied. Kutward potassium currents in RGC represented by populations of slow inactivating and non-inactivating currents. Inward sodium currents were completely blocked by extracellular application of 0.25 mM TTX. Calcium conductance in freshly isolated RGC has two components: low- and high-threshold. Extracellular application of nifedipine (10 mM) or Cd2+ (10 mM) blocked high threshold calcium currents by 28% and 60%, correspondingly, without any significant effect on low threshold calcium currents.

[Substantiation of application of the anterior trans-pyramidal approach in skull base tumors]. / Obhruntuvannia zastosuvannia perednikh transpiramidnykh dostupiv do pukhlyn osnovy cherepa.

The microtopographic-anatomic substantiation of anterior transpyramid approaches to the skull base tumors was conducted. The transpyramid approaches introduction in clinical practice had permitted to improve surgical treatment results in patients with the difficult of access skull base tumors. Indications and choice of approach depending on the kind, localization and tumor spread in the skull base in the temporal bone pyramid part were substantiated.