60 research outputs found
Frequency-modulated electromagnetic neural stimulation (FREMS) as a treatment for symptomatic diabetic neuropathy: results from a double-blind, randomised, multicentre, long-term, placebo-controlled clinical trial
AIMS/HYPOTHESIS: The aim was to evaluate the efficacy and safety of
transcutaneous frequency-modulated electromagnetic neural stimulation (frequency
rhythmic electrical modulation system, FREMS) as a treatment for symptomatic
peripheral neuropathy in patients with diabetes mellitus.
METHODS: This was a double-blind, randomised, multicentre, parallel-group study
of three series, each of ten treatment sessions of FREMS or placebo administered
within 3 weeks, 3 months apart, with an overall follow-up of about 51 weeks. The
primary endpoint was the change in nerve conduction velocity (NCV) of deep
peroneal, tibial and sural nerves. Secondary endpoints included the effects of
treatment on pain, tactile, thermal and vibration sensations. Patients eligible
to participate were aged 18-75 years with diabetes for ≥ 1 year, HbA(1c) <11.0%
(97 mmol/mol), with symptomatic diabetic polyneuropathy at the lower extremities
(i.e. abnormal amplitude, latency or NCV of either tibial, deep peroneal or sural
nerve, but with an evocable potential and measurable NCV of the sural nerve), a
Michigan Diabetes Neuropathy Score ≥ 7 and on a stable dose of medications for
diabetic neuropathy in the month prior to enrolment. Data were collected in an
outpatient setting. Participants were allocated to the FREMS or placebo arm (1:1
ratio) according to a sequence generated by a computer random number generator,
without block or stratification factors. Investigators digitised patients' date
of birth and site number into an interactive voice recording system to obtain the
assigned treatment. Participants, investigators conducting the trial, or people
assessing the outcomes were blinded to group assignment.
RESULTS: Patients (n = 110) with symptomatic neuropathy were randomised to FREMS
(n = 54) or placebo (n = 56). In the intention-to-treat population (50 FREMS, 51
placebo), changes in NCV of the three examined nerves were not different between
FREMS and placebo (deep peroneal [means ± SE]: 0.74 ± 0.71 vs 0.06 ± 1.38 m/s;
tibial: 2.08 ± 0.84 vs 0.61 ± 0.43 m/s; and sural: 0.80 ± 1.08 vs -0.91 ± 1.13
m/s; FREMS vs placebo, respectively). FREMS induced a significant reduction in
day and night pain as measured by a visual analogue scale immediately after each
treatment session, although this beneficial effect was no longer measurable 3
months after treatment. Compared with the placebo group, in the FREMS group the
cold sensation threshold was significantly improved, while non-significant
differences were observed in the vibration and warm sensation thresholds. No
relevant side effects were recorded during the study.
CONCLUSIONS/INTERPRETATION: FREMS proved to be a safe treatment for symptomatic
diabetic neuropathy, with immediate, although transient, reduction in pain, and
no effect on NCV.
TRIAL REGISTRATION: ClinicalTrials.gov NCT01628627.
FUNDING: The clinical trial was sponsored by Lorenz Biotech (Medolla, Italy),
lately Lorenz Lifetech (Ozzano dell'Emilia, Italy)
The Stringent Response and Cell Cycle Arrest in Escherichia coli
The bacterial stringent response, triggered by nutritional deprivation, causes an accumulation of the signaling nucleotides pppGpp and ppGpp. We characterize the replication arrest that occurs during the stringent response in Escherichia coli. Wild type cells undergo a RelA-dependent arrest after treatment with serine hydroxamate to contain an integer number of chromosomes and a replication origin-to-terminus ratio of 1. The growth rate prior to starvation determines the number of chromosomes upon arrest. Nucleoids of these cells are decondensed; in the absence of the ability to synthesize ppGpp, nucleoids become highly condensed, similar to that seen after treatment with the translational inhibitor chloramphenicol. After induction of the stringent response, while regions corresponding to the origins of replication segregate, the termini remain colocalized in wild-type cells. In contrast, cells arrested by rifampicin and cephalexin do not show colocalized termini, suggesting that the stringent response arrests chromosome segregation at a specific point. Release from starvation causes rapid nucleoid reorganization, chromosome segregation, and resumption of replication. Arrest of replication and inhibition of colony formation by ppGpp accumulation is relieved in seqA and dam mutants, although other aspects of the stringent response appear to be intact. We propose that DNA methylation and SeqA binding to non-origin loci is necessary to enforce a full stringent arrest, affecting both initiation of replication and chromosome segregation. This is the first indication that bacterial chromosome segregation, whose mechanism is not understood, is a step that may be regulated in response to environmental conditions
Cell Size and the Initiation of DNA Replication in Bacteria
In eukaryotes, DNA replication is coupled to the cell cycle through the actions of cyclin-dependent kinases and associated factors. In bacteria, the prevailing view, based primarily from work in Escherichia coli, is that growth-dependent accumulation of the highly conserved initiator, DnaA, triggers initiation. However, the timing of initiation is unchanged in Bacillus subtilis mutants that are ∼30% smaller than wild-type cells, indicating that achievement of a particular cell size is not obligatory for initiation. Prompted by this finding, we re-examined the link between cell size and initiation in both E. coli and B. subtilis. Although changes in DNA replication have been shown to alter both E. coli and B. subtilis cell size, the converse (the effect of cell size on DNA replication) has not been explored. Here, we report that the mechanisms responsible for coordinating DNA replication with cell size vary between these two model organisms. In contrast to B. subtilis, small E. coli mutants delayed replication initiation until they achieved the size at which wild-type cells initiate. Modest increases in DnaA alleviated the delay, supporting the view that growth-dependent accumulation of DnaA is the trigger for replication initiation in E. coli. Significantly, although small E. coli and B. subtilis cells both maintained wild-type concentration of DnaA, only the E. coli mutants failed to initiate on time. Thus, rather than the concentration, the total amount of DnaA appears to be more important for initiation timing in E. coli. The difference in behavior of the two bacteria appears to lie in the mechanisms that control the activity of DnaA
Thiosaccharine disulfide: synthesis, crystal structure, spectroscopic characterization and theoretical study
The title compound, (thiosaccharine disulfide), bis[1,10dioxide-2,3-dihidro-1,2-benzoisothiazol]disulfide, (tsac)2 has been synthesized and fully characterized by UV–Visible, IR, Raman, 1H and 13C NMR spectroscopy elemental analysis and structural X-ray crystallography. A DFT theoretical study has been performed and good agreement between experimental and theoretical values of structural parameters and vibration frequencies have been achieved.Universidad Nacional del Sur (UNS) - SecretarÃa General de Ciencia y TecnologÃa (SGCyT) (M24/Q043)CONICETFAPES
A two-year longitudinal study on strain and needs in caregivers of advanced ALS patients
Biochemical and physiological mechanisms related to cold acclimation and enhanced freezing tolerance in poplar plantlets
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