The local peripheral combination of analgesic drugs with herbal derivatives may have beneficial effects. Information on the action mechanism of these interactions between drugs is scarce. Therefore, ...the main of the present study was to determine the pharmacological interaction and action mechanism of the combination α-Bisabolol and diclofenac.
Rats were injected in the dorsal surface of the right hind paw with 1% formalin. Rats received subcutaneous injections in the dorsal surface of paw of vehicles or increasing doses of α-Bisabolol, diclofenac or their combination before formalin injection into the paw. Antinociception of the α-Bisabolol + diclofenac combination was evaluated with and without the local treatment of naloxone, metformin, NG-nitro-L-arginine methyl ester (L-NAME), 1H- (1,2,4)-oxadiazolo (4,2-a) quinoxalin-1-one (ODQ), glibenclamide, glipizide, 4-aminopyridine, tetraethylammonium, apamin, or charybdotoxin.
α-Bisabolol, diclofenac or α-Bisabolol-diclofenac combinations produced significant antinociception in the rat (
< 0.05). The experimental effective dose (ED) value of 109.2 µg/paw was different significantly of the theoretical effective dose (ED) of 245.7 µg/paw (synergism). Blockers significantly reverted the antinociception produced by the synergistic combination of α-Bisabolol and diclofenac.
Data showed a synergism of the α-Bisabolol-diclofenac combination and the activation of the opioid receptor-Nitric Oxide-cyclic GMP-K
channels pathway and a biguanide-dependent mechanism in order to produce the potentiation of its peripheral antinociception in the formalin test.
Abstract Objective To evaluate the prevalence, impact and treatment of primary dysmenorrhea among Mexican university students. Study design A multiple-choice questionnaire was administered to 1539 ...students in six university programs: medicine, nursing, nutrition, dentistry, pharmacy and psychology. Data on the presence, severity, symptoms, treatment and limitations caused by dysmenorrhea were obtained and analyzed. Results The mean ± SD age of the women was 20.4 ± 2.0 years; the mean age of menarche was 12.3 ± 1.5 years. A total of 64% of the women experienced dysmenorrhea. Dysmenorrhea was more prevalent among nutrition and psychology students than among medicine, pharmacy and dentistry students ( p < 0.05). Dysmenorrhea was mild in 36.1% of women, moderate in 43.8% and severe in 20.1%. Nursing students showed an intensity of pain that was significantly higher than that of medicine and dentistry students ( p < 0.05). Sixty-five percent of the women with dysmenorrhea reported that it limited their daily activities, and 42.1% reported school absenteeism (SA) as a result. Of those who experienced dysmenorrhea, 25.9% consulted a physician, and 61.7% practiced self-medication (SM). The most common medications used were an over-the-counter (OTC) medication with paracetamol (an analgesic), pamabrom (a diuretic), and pyrilamine (a histamine antagonist), another OTC with metamizol (a non-steroidal anti-inflammatory drug NSAID) plus butylhioscine (an antispasmodic drug) and naproxen (a NSAID). Of those women using prescribed medications, 18.4% reported complete remission of their symptoms, while 78.1% reported little to moderate alleviation, and 3.6% reported no effect on their menstrual distress. Similarly, of the women who practiced SM, 23.4% reported complete relief, 75.5% reported little to moderate effectiveness, and 1.0% reported no efficacy. Conclusion The prevalence of dysmenorrhea among Mexican university students is high, and the pain that these women suffer can be severe, disabling and result in short-term SA. The pain is often not completely relieved despite the use of medication. It is necessary to improve the therapeutic options for relief of pain caused by dysmenorrhea and to minimize the impact of dysmenorrhea on social, economic and school activities.
Experiments using nonsteroidal anti-inflammatory drugs (NSAIDs) alone have produced limited antinociceptive effects in animal models. For this reason, the number of studies involving the ...administration of NSAIDs along with an adjuvant drug harboring different mechanisms of action has increased enormously. Here, combinations of diclofenac and pyrilamine were used to determine their influence on nociception (formalin test), inflammation (paw inflammation produced by carrageenan), and gastric damage in rodents. Diclofenac, pyrilamine, or combinations of diclofenac and pyrilamine produced antinociceptive and anti-inflammatory effects in the rat. The systemic administration of diclofenac alone and in combination with pyrilamine produced significant gastric damage. Effective dose (ED) values were determined for each individual drug, and isobolograms were prepared. The theoretical ED values for the antinociceptive (systemic, 35.4 mg/kg; local, 343.4 μg/paw) and the anti-inflammatory (37.9 mg/kg) effects differed significantly from the experimental ED values (systemic antinociception, 18.1 mg/kg; local antinociception, 183.3 μg/paw; anti-inflammation, 10.6 mg/kg). Therefore, it was concluded that the interactions between diclofenac and pyrilamine are synergistic. The data suggest that the diclofenac–pyrilamine combinations can interact at the systemic and local peripheral levels, thereby offering a therapeutic alternative for the clinical management of inflammatory pain.
Background: Dysmenorrhea is a menstrual condition characterized by severe and frequent pain related to menstruation. Primary dysmenorrhea is a major problem worldwide since its prevalence ranges from ...28% to 94% in some populations. Studies in specific populations of changes in the prevalence of dysmenorrhea over time have been scarce. Therefore, the aim of the present study was to compare the prevalence and characteristics of primary dysmenorrhea between two independent populations of Mexican university women over time (2010 versus 2020). Methods: An anonymous multiple-choice questionnaire was completed by two independent groups of students. Variables from the two studies were extracted and compared between them. The degree of dysmenorrheic pain was assessed by a 100 mm visual analog scale (VAS) ranging from “no pain” to “the worst pain imaginable”. Study A included 1539 women (published in 2010), and Study B included 2154 women (realized in 2020). Results: A total of 3693 students were surveyed. Dysmenorrhea prevalence was established in 62.4% (n = 961) in survey A and 78.9% (n = 1699) in survey B (p < 0.05). The pain means were 54.1 ± 23.4 mm and 64.0 ± 20.6 mm for Studies A and B, respectively (p < 0.05). Moderate-severe pain was reported by 753 (78.4%) women in Study A and 1546 (91.0%) women in Study B. Significantly more students from Study B (90.4%) had limitations in daily activities due to dysmenorrhea compared to women from Study A (65.0%) (p < 0.05). School absenteeism in Study B (50.6%) was significantly higher than that in Study A (27.4%) (p < 0.05). Conclusions: The prevalence of primary dysmenorrhea and the presence of symptoms in students showed statistically significant increases over time (2010 versus 2020). Similarly, due to the symptoms of dysmenorrhea, school absenteeism increased significantly, and daily activities were progressively affected.
Pamabrom is a diuretic that is effective in treating premenstrual syndrome and primary dysmenorrhea. The aim of this study was to examine the effect of metformin and modulators of the opioid ...receptor-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-K
channel pathway on the local antinociception induced by pamabrom. The rat paw 1% formalin test was used to assess the effects. Rats were treated with local administration of pamabrom (200-800 µg/paw) or indomethacin (200-800 µg/paw). The antinociception of pamabrom or indomethacin was evaluated with and without the local pretreatment of the blockers. Local administration of pamabrom and indomethacin produced dose-dependent antinociception during the second phase of the test. Local pretreatment of the paws with naloxone (50 µg/paw), l-nitro-arginine methyl ester (10-100 µg/paw), or 1
-(1,2,4)-oxadiazolo4,2-
quinoxalin-1-one (10-100 µg/paw) reverted the antinociception induced by local pamabrom, but not of indomethacin. Similarly, the K
channel blockers glibenclamide, glipizide, 4-aminopyridine, tetraethylammonium, charybdotoxin, or apamin reverted the pamabrom-induced antinociception, but not of indomethacin. Metformin significantly blocked the antinociception of pamabrom and indomethacin. Our data suggest that pamabrom could activate the opioid receptor-NO-cGMP-K
channel pathway to produce its peripheral antinociception in the formalin test. Likewise, a biguanide-dependent mechanism could be activated by pamabrom and indomethacin to generate antinociception.
The aim of this study was to examine if the peripheral antinociceptive effects of the opioid agonist/antagonist nalbuphine and buprenorphine involve the sequential participation of nitric oxide (NO) ...and cyclic guanosine monophosphate (cGMP) synthesis followed by K
+
channel opening in the formalin test. Wistar rats (180–220 g) were injected in the dorsal surface of the right hind paw with formalin (1%). Rats received a subcutaneous (s.c.) injection into the dorsal surface of the paw of vehicles or increasing doses of nalbuphine (50–200 μg/paw) or buprenorphine (1–5 μg/paw) 20 min before formalin injection into the paw. Nalbuphine antinociception was reversed by the s.c. injection into the paw of the inhibitor of NO synthesis (N
G
-nitro-
l
-arginine methyl ester (L-NAME)), by the inhibitor of guanylyl cyclase (1H-1,2,4oxadiazolo4,3-aquinoxalin-1-one (ODQ)), by the K
ir
6.1–2, ATP-sensitive K
+
channel inhibitors (glibenclamide and glipizide), by the K
Ca
2.1–3, small conductance Ca
2+
-activated K
+
channel blocker (apamin), by the K
Ca
1.1, large conductance Ca
2+
-activated K
+
channel blocker (charybdotoxin), and by the K
V
, voltage-dependent K
+
channel inhibitors (4-aminopyridine (4-AP) and tetraethylammonium chloride (TEA)). The antinociceptive effect produced by buprenorphine was blocked by the s.c. injection of 4-AP and TEA but not by L-NAME, ODQ, glibenclamide, glipizide, apamin, or charybdotoxin. The present results provide evidence for differences in peripheral mechanisms of action between these opioid drugs.
Studying the behavioral response of blood-sucking disease-vector insects to potentially repellent volatile compounds could shed light on the development of new control strategies. Volatiles released ...by human facial skin microbiota play different roles in the host-seeking behavior of triatomines. We assessed the repellency effect of such compounds of bacterial origin on Triatoma infestans and Rhodnius prolixus, two important vectors of Chagas disease in Latin America.
Using an exposure device, insects were presented to human odor alone (control) and in the presence of three individual test compounds (2-mercaptoethanol, dimethyl sulfide and 2-phenylethanol, the latter only tested in R. prolixus) and the gold-standard repellent NN-diethyl-3-methylbenzamide (DEET). We quantified the time the insects spent in the proximity of the host and determined if any of the compounds evaluated affected the behavior of the insects.
We found volatiles that significantly reduced the time spent in the proximity of the host. These were 2-phenylethanol and 2-mercaptoethanol for R. prolixus, and dimethyl sulfide and 2-mercaptoethanol for T. infestans. Such an effect was also observed in both species when DEET was presented, although only at the higher doses tested.
The new repellents modulated the behavior of two Chagas disease vectors belonging to two different triatomine tribes, and this was achieved using a dose up to three orders of magnitude lower than that needed to evoke the same effect with DEET. Future efforts in understanding the mechanism of action of repellent compounds such as 2-mercaptoethanol, as well as an assessment of their temporal and spatial repellent properties, could lead to the development of novel control strategies for these insect vectors, refractory to DEET.
Chagas disease is considered to be endemic in up to 40% of the territory of Colombia, and to date 27 triatomine species have been reported the country. The purpose of this study was to update the ...geographical distribution of triatomine species in Colombia and assess the species richness patterns and their altitudinal distribution.
Occurrence data were compiled between 2007 and 2020, including from reports of entomological surveillance from the Instituto Nacional de Salud (INS), the Centro de Investigaciones en Microbiología y Parasitología Tropical (CIMPAT) at Universidad de Los Andes and a review of the literature. Geographic Information Systems (GIS) were used to describe general species richness patterns of the Triatominae subfamily. To establish the altitudinal distribution of the triatomine species, ranges were obtained from reports with unique elevation values. A generalized linear model was fitted, based on a Poisson distribution, to test the relation between triatomine species richness and Chagas disease cases (2012-2019).
An updated geographical and altitudinal distribution for triatomine species in Colombia was established, with 507 municipalities added to the previously known distributions. The greatest triatomine richness in Colombia was found to be concentrated in the northeastern region of the country, extending towards the center to the departments of Arauca, Casanare and Meta. Regarding the altitudinal distribution, the study revealed that the species Rhodnius prolixus and Triatoma dimidiata have the greatest altitudinal ranges. The data also suggest a positive relation between species richness and number of Chagas disease cases reported per department.
Altitudinal ranges for 17 triatomine species found in Colombia are presented. Species richness and species composition patterns are also described, and areas with a higher risk of transmission based on the relation found with Chagas disease cases are highlighted. This updated distribution reveals that Panstrongylus geniculatus is the triatomine with the largest presence by municipalities in Colombia, being reported in 284 municipalities, followed by Rhodnius prolixus in 277 municipalities.
The present study aimed to determine the effectiveness of sclerotherapy using NBCA (Histoacryl Blue®; B. Braun, Melgungen, Germany), with or without hydrodissection, for the treatment of simple renal ...cysts. Materials and Methods: Patients who presented to an interventional radiology clinic for the diagnosis of symptomatic renal cysts which had previously been identified at an outpatient clinic were selected for inclusion in this study. A total of 28 patients were randomly divided into 2 groups, based on whether or not they underwent hydrodissection along with ultrasound-guided NBCA-based sclerotherapy. Sonographs were performed at 0, 7, and 180 days post-procedure to record the residual volume of the renal cysts and to determine the efficacy of the procedure. Results: A total of 32 cysts in 28 patients were treated with sclerotherapy, 18 (64%) females and 10 (36%) males. The average age of the patients was 61.8 years (range: 33–89 years). All patients reported an improvement in symptoms associated with the existing renal cysts at 7 and 180 days post-procedure, and at 7 days post-procedure a statistically significant reduction in cyst volume was observed (all patients: 96.8%; group A: 96%; group B: 97.6%). The reduced cyst volume was still observed 180 days post-procedure (all patients: 98.6%; group A: 98.2%; group B: 98.9%). There was no significant difference between the two treatment groups. Conclusion: There is a significant and persistent reduction in the volume of renal cysts, in addition to an improvement of the associated symptoms, after treatment with NBCA-based sclerotherapy, with or without hydrodissection.
•Chlorella vulgaris and Microcystis sp. (MS) removed 78.7% and 88.4% phosphorous (P).•91.5% P was recovered from MS to MS-derived hydrochar produced at 260 °C (MSHCA260).•Microalgal hydrochars slowly released P and improved soil P availability.•MSHCA260 increased P use efficiency and wheat yield compared to chemical Fertilizer.•Microalgae and hydrochar technology recycled P from wastewater to crop food.
The objective of the present study was to scrutinize the effect of nitric oxide (NO), cyclic GMP (cGMP), potassium channel blockers, and metformin on the citral-produced peripheral antinociception. ...The rat paw 1% formalin test was used to assess nociception and antinociception. Rats were treated with local peripheral administration of citral (10–100 µg/paw). The antinociception of citral (100 µg/paw) was evaluated with and without the local pretreatment of naloxone, NG-L-nitro-arginine methyl ester (L-NAME, a NO synthesis inhibitor), 1H-(1,2,4)-oxadiazolo(4,2-a)quinoxalin-1-one (ODQ, a soluble guanylyl cyclase inhibitor), metformin, opioid receptors antagonists, and K
+
channel blockers. Injection of citral in the rat paw significantly decreased the nociceptive effect of formalin administration during the two phases of the test. Local pretreatment of the paws with L-NAME and ODQ did not reduced the citral-induced antinociception. Glipizide or glibenclamide (K
ir
6.1-2; ATP-sensitive K
+
channel blockers), tetraethylammonium or 4-aminopyridine (K
V
; voltage-gated K
+
channel blockers), charybdotoxin (K
Ca
1.1; big conductance calcium-activated K
+
channel blocker), apamin (K
Ca
2.1-3; small conductance Ca
2+
-activated K
+
channel antagonist), or metformin, but not the opioid antagonists, reduced the antinociception of citral. Citral produced peripheral antinociception during both phases of the formalin test. These effects were due to the activation of K
+
channels and a biguanide-dependent mechanism.
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