7 research outputs found
The effect of insulin and sulodexide (Vessel Due F) on diabetic foot syndrome. Pilot study in elderly patients
Celem pracy była ocena skuteczności stosowania insuliny wraz z sulodeksydem (mieszanina
80% pochodnych heparyny i 20% siarczanu dermatanu) w leczeniu owrzodzeń stóp oraz
określenie ich wpływu na mikrokrążenie skórne i neuropatię cukrzycową. Chorzy
z zaawansowaną neuropatią cukrzycową i owrzodzeniem stopy losowo przydzielono
do grupy leczonej insuliną (I) z sulodeksydem (S) (n = 12) lub do grupy kontrolnej
leczonej insuliną z placebo (P) (n = 6) przez 10 tygodni. Za pomocą metody dopplerowskiego
lasera oceniano skórny przepływ krwi w stopach (LDF, laser doppler flow)
w spoczynku oraz po 30- i 60-sekundowym niedokrwieniu. Ocenie poddano również
przewodnictwo nerwowe
na podstawie czuciowych i ruchowych potencjałów wywołanych. U chorych na cukrzycę
skórny przepływ po niedokrwieniu był 2,5 raza krótszy w kończynie z owrzodzeniem niż w stopie zdrowej. Obserwowano
znamienny wzrost przepływów skórnych po 30-
i 60-sekundowym niedokrwieniu po zakończeniu terapii
(grupa IS, owrzodzenie stopy, LDF - 60 s; od
99,1 ± 14,3 do 218,6 ± 28,6 PU, p < 0,001, grupa
od 110,5 ± 13,0 do 164,8 ± 15,4 PU, p < 0,05). Czas
przekrwienia reaktywnego uległ wydłużeniu w grupie
IS (IS: od 30,3 ± 2,9 do 43,9 ± 2,2 s, p < 0,001; IP:
od 28,7 ± 3,0 do 33,3 ± 3,3 s, NS). W grupie IS 92%
owrzodzeń stóp uległo zagojeniu w ciągu 46,4 dnia,
natomiast w grupie IP 83% w ciągu 63,0 dnia. Badania
przewodnictwa nerwowego nie wykazały różnic
nasilenia neuropatii w obrębie grup i pomiędzy
grupami. W stopach z owrzodzeniami sulodeksyd i
insulina poprawiają przepływ skórny w odpowiedzi
na niedokrwienie, nie wpływając na przewodnictwo
nerwowe. Kliniczne efekty działania sulodeksydu, sumując
się z działaniami insuliny, mogą istotnie skracać
czas niezbędny do całkowitego wyleczenia
owrzodzenia. Ostateczne potwierdzenie przedstawionych
wstępnych wyników wymaga dalszych badań
klinicznych.To assess the efficacy of insulin plus sulodexide
(a mixture of 80% heparin-like substances and 20%
dermatan sulphate) on diabetic ulcers, and its influence
on foot skin microcirculation and diabetic neuropathy.
Two groups of diabetic patients, suffering
from severe neuropathy and ulceration, were randomly
assigned to insulin (I) plus sulodexide (S)
(n = 12) or insulin plus placebo (P) (n = 6) therapy,
for 10 weeks. Laser Doppler assessment of foot skin
flow (LDF), at rest and 30 or 60 s after arterial occlusion,
and nerve conduction tests (sensorial evoked
and motoric conduction potentials) have been evaluated
in both groups. Postischaemic flow was 2.5
times shorter in ulcerated vs. non-ulcerated feet in
diabetic patients. A significant increase in flows after
30 and 60 s ischaemia was detected in both groups
at the end of therapy (IS group, ulcerated foot, LDF
= 60 s: from 99.1 ± 14.3 to 218.6 ± 28.6 PU, P <
0.001. IP group = from 110.5 ± 13.0 to 164.8 ± 15.4
PU, P < 0.05). The length of reactive hyperaemia was
higher in IS vs. IP group (IS: from 30.3 ± 2.9 to 43.9
± 2.2 s, P < 0.001; IP: from 28.7 ± 3.0 to 33.3 ± 3.3 s,
ns). Ninety-two percent of ulcers heals in a mean time
of 46.4 days (IS group) vs. 83% and 63.0 days, respectively,
in IP group. Nerve conduction studies have
not demonstrated within- and between-group differences.
Sulodexide and insulin improve the postischaemic
skin flow in ulcerated feet, without affecting
nerve conduction tests. The effect of sulodexide results
additive to insulin; it is clinically relevant, in the
view of the possibility of reducing the time needed
to completely heal ulcers. The ultimate validation of
these preliminary results requires extensive trials
Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection
BACKGROUND Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy. Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively. METHODS We conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis. The primary end point was recurrent infection (new episode after initial clinical cure) within 12 weeks after infusion in the modified intention-to-treat population. RESULTS In both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo (MODIFY I: 17% [67 of 386] vs. 28% [109 of 395]; adjusted difference, −10.1 percentage points; 95% confidence interval [CI], −15.9 to −4.3; P<0.001; MODIFY II: 16% [62 of 395] vs. 26% [97 of 378]; adjusted difference, −9.9 percentage points; 95% CI, −15.5 to −4.3; P<0.001) and was significantly lower with actoxumab plus bezlotoxumab than with placebo (MODIFY I: 16% [61 of 383] vs. 28% [109 of 395]; adjusted difference, −11.6 percentage points; 95% CI, −17.4 to −5.9; P<0.001; MODIFY II: 15% [58 of 390] vs. 26% [97 of 378]; adjusted difference, −10.7 percentage points; 95% CI, −16.4 to −5.1; P<0.001). In prespecified subgroup analyses (combined data set), rates of recurrent infection were lower in both groups that received bezlotoxumab than in the placebo group in subpopulations at high risk for recurrent infection or for an adverse outcome. The rates of initial clinical cure were 80% with bezlotoxumab alone, 73% with actoxumab plus bezlotoxumab, and 80% with placebo; the rates of sustained cure (initial clinical cure without recurrent infection in 12 weeks) were 64%, 58%, and 54%, respectively. The rates of adverse events were similar among these groups; the most common events were diarrhea and nausea. CONCLUSIONS Among participants receiving antibiotic treatment for primary or recurrent C. difficile infection, bezlotoxumab was associated with a substantially lower rate of recurrent infection than placebo and had a safety profile similar to that of placebo. The addition of actoxumab did not improve efficacy. (Funded by Merck; MODIFY I and MODIFY II ClinicalTrials.gov numbers, NCT01241552 and NCT01513239.
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Gastrointestinal secretory, motor and circulatory effects of corticotropin releasing factor (CRF)
This study was designed to determined the effects of CRF on the gastrointestinal functions such as secretion, motility and circulation in dogs. CRF was found to inhibit dose-dependently gastric acid response to pentagastrin but not to histamine. CRF stimulated pancreatic bicarbonate and protein secretion under basal conditions and in response to secretin or cholecystokinin (CCK). This stimulation was accompanied by an increase in plasma levels of pancreatic polypeptide (PP), but not of secretin or gastrin. CRF caused a partial inhibition of the migrating motor complexes in fasted dogs and increased spike activity of the small bowel. These motor effects of CRF probably resulted from the action of the released PP on the intestinal smooth muscle. CRF is also a potent and selective stimulant of the mesenteric blood flow. This effect may be secondary to the stimulation of intestinal motility and metabolism
Identification and Characterization of Carprofen as a Multitarget Fatty Acid Amide Hydrolase/Cyclooxygenase Inhibitor
Pain and inflammation are major therapeutic areas for drug discovery. Current drugs for these pathologies have limited efficacy, however, and often cause a number of unwanted side effects. In the present study, we identify the nonsteroidal anti-inflammatory drug carprofen as a multitarget-directed ligand that simultaneously inhibits cyclooxygenase-1 (COX-1), COX-2, and fatty acid amide hydrolase (FAAH). Additionally, we synthesized and tested several derivatives of carprofen, sharing this multitarget activity. This may result in improved analgesic efficacy and reduced side effects (Naidu et al. J. Pharmacol. Exp. Ther.2009, 329, 48-56; Fowler, C. J.; et al. J. Enzyme Inhib. Med. Chem.2012, in press; Sasso et al. Pharmacol. Res.2012, 65, 553). The new compounds are among the most potent multitarget FAAH/COX inhibitors reported so far in the literature and thus may represent promising starting points for the discovery of new analgesic and anti-inflammatory drugs