This study aimed to compare the activities of the antioxidant enzymes glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT), as well as reduced glutathione (GSH), lipid peroxidation (MDA), and serum biochemistry parameters in pregnant (P+, n = 13) and non-pregnant (P-, n = 7) bitches in order to elucidate physiological changes in oxidative status associated with pregnancy. Ultrasonography controls were performed on days 25, 35, 45, and 55 in both groups; additionally, a final examination was conducted one day after parturition (PP1) in P+ or day 63 (d63) in P-. Blood samples were collected on day 12 post-ovulation and subsequently in parallel with each ultrasonographic evaluation. On day 55, GPx, SOD and CAT activities, as well as MDA levels were significantly higher in the P+ group compared with the P- group (p < 0.05; p < 0.01). No significant differences were found in GSH concentrations between P+ and P-. Across sampling days, no significant differences were detected in SOD and MDA levels within the P+ group or in GPx and MDA levels within the P- group. No significant correlations were detected between enzyme activities, lipid peroxidation, and antioxidant parameters. The findings indicate that oxidative stress and antioxidant defense mechanisms increase at different stages of normal canine pregnancy, reflecting a physiological adaptation that supports the maintenance of pregnancy.

Heat shock proteins (HSPs) fulfil protective tasks in the whole organism; in pregnant dogs, they are expressed in the ovary, placenta and preimplantation embryo. Our objective was to compare the expression of HSP60 and -70, along with indicators of proliferation and apoptosis, in the non-pregnant and pregnant uterus/placenta and ovaries. Tissues were obtained after ovariohysterectomy and examined by means of immunohistochemistry. There were differences between pregnant and non-pregnant tissues: the expression level of HSP70 during preimplantation in superficial cells was significantly lower than that in early diestrus, with similar results observed for Ki67. The immunosignal for HSP70 was significantly decreased during the postimplantation stage in almost all cell types, whilst the number of HSP60-positive cells did not change. In pregnant animals, the number of Ki67-positive cells significantly increased until the postimplantation stage. In the placenta and trophoblast, the expression of HSP60 and -70 was strong, while no HSP70 signal was detected in endometrial epithelial cells. The caspase 3 immunosignal in the uterus and placenta was generally weak. In the corpora lutea, HSP60, HSP70 and caspase 3 were mainly detected in theca lutein cells, while no signal for KI67 was seen. In follicles, caspase 3 and KI67 expression was low, except in granulosa cells of tertiary follicles and oocytes. We conclude that the different expression of HSPs in pregnant and non-pregnant animals may point towards different regulatory and/or protective tasks.

In brief:The role of inflammation in the regulation of pregnancy remains poorly understood in dogs. Findings from this study propose the involvement of IL1β signaling during early embryo-maternal interactions in the dog, while in vitro effects suggest it may disrupt decidual cell function in the canine mature placenta. Abstract:Although implantation and parturition are associated with pro-inflammatory signals, inflammatory responses in the mature placenta frequently lead to pregnancy loss. Indeed, uterine inflammatory/infectious diseases are major causes of infertility and pregnancy loss in dogs. The pro-inflammatory interleukin (IL)-1β is increased during canine placentation and downregulated in mature placentae during healthy pregnancies but is enriched in the placenta during infectious events. Furthermore, canine pregnancy success is linked with decidual cells, the only placental cells expressing the nuclear progesterone receptor. This study assessed utero-placental abundance of IL1β receptor 1 (IL1R1) throughout canine pregnancy and possible modulatory effects of IL1β on decidualization. The mRNA levels of IL1R1 were increased in mature mid-gestation placentae and at term (P < 0.05). Immunohistochemistry co-localized IL1β and IL1R1 in the trophoblast during early placentation, implicating IL1β-signaling in early embryo-maternal communication. In the mature placenta, IL1R1 was localized, i.a. in decidual cells. In vitro, IL1β had low modulatory effects on PGE2- and/or P4-stimulated dog uterine stromal (DUS) cells, implying a relatively weak impact of this interleukin in the decidualization process. However, in DUS cells decidualized with cAMP, IL1β decreased transcriptional amounts of selected decidualization markers IGF1, PTGS2 and PTGES, as well as ECM1 and TIMP2 (P < 0.001). Transcriptional and protein availabilities of CX43, a gap junction component, were also decreased by IL1β (P < 0.001). These findings support a dual role for IL1β in canine pregnancy: involvement in early embryo-maternal communication during its establishment and disturbing placental homeostasis by disrupting decidual cell function in fully developed placenta.

This study aimed to evaluate the effects of Kisspeptin (KP-10) and Cabergoline (CB) on hormonal regulation in anestrus female dogs. Twenty-three clinically healthy anestrus female dogs were randomly allocated into five treatment groups. Group 1 (G1, n = 4) received CB with saline; Group 2 (G2, n = 4) received 0.5 μg/kg KP-10 + CB; Group 3 (G3, n = 5) received 1 μg/kg KP-10 + CB; Group 4 (G4, n = 5) received 0.5 μg/kg KP-10 alone; and Group 5 (G5, n = 5) received 1 μg/kg KP-10 alone. KP-10 was administered intravenously as a single dose, while CB was given orally for 15 consecutive days. Blood samples were collected at multiple time points to measure serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), and progesterone (P4). Results showed that LH and FSH concentrations increased significantly in a dose-dependent manner in groups receiving KP-10 alone (G4, G5), with G2 showing the lowest increase. Only G3 exhibited a P4 increase above 2 ng/mL on day 15, suggesting possible luteinization. CB alone (G1) had minimal effects on hormone levels. E2 levels increased in all groups, although not reaching proestrus levels. KP-10, particularly at 1 μg/kg (G3, G5), effectively stimulated LH and FSH release but did not induce clinical estrus. The short-term CB regimen was insufficient, emphasizing the need for an extended duration of administration. KP-10 alone appears promising for inducing gonadotropin release; however, in the absence of proestrus bleeding or behavioral signs of estrus, its efficacy in triggering a complete estrous response remains uncertain. Further research is needed to clarify whether the observed hormonal changes can induce clinical estrus.

Although dogs lack the classical pregnancy recognition via embryo-derived anti-luteolytic signaling, precise embryo-maternal communication remains essential in establishing pregnancy. While previous studies confirmed uterine responses to pre-attachment embryos versus semen-exposed non-pregnant controls, they did not include non-mated, non-pregnant controls. Following the hypothesis that embryo-derived signaling differs from the responses induced by semen, the present project included three groups of dogs (d. 10-12 of pregnancy/corresponding dioestrus): non-mated, mated and pregnant, and mated but non-pregnant (semen-exposed). The expression of nuclear hormone receptors and selected immunomodulatory factors was detected using semi-quantitative PCR and immunohistochemistry. While transcript levels of the progesterone (P4) nuclear receptor (PGR) were significantly elevated in response to embryo presence, its staining across the endometrial layers indicated apparent effects of semen exposure, further potentiated by the presence of embryos. ESR1/ERα showed a clear embryo-driven response, whereas ESR2/ERβ remained unchanged. The decreased availability of FOXP3 transcripts in response to semen, and the consistent expression of CD4 and CD25, suggests an increased presence of T-helper (Th) cells. Semen exposure also resulted in higher levels of CD163 and CD206, and decreased expression of CD8. Embryos had a stimulatory effect on the joint expression of T-cell markers (FOXP3, CD4, and CD25), pointing toward T-regs activity. Embryos also increased DLA-DRA and NCR1 expression. This study underscores the importance of differentiating between seminal plasma- and embryo-driven signals in the canine uterus. While exposure to semen may help prepare the uterus for implantation by modulating the immune response, embryo-derived signals further modulate these effects.

The study groups (n = 39) included ewes with ongoing pregnancy (P+; n = 19), with fetal death (FD; n = 12), and that were not pregnant (P-; n = 8). Blood samples were taken on days 10, 20, 30, 40, 60, 80, and 150 post-mating. Ultrasonography (USG) controls started on day 30. The P4 concentrations differed significantly between P+ and P- on all days (p < 0.001). Regarding AMH concentrations, a significant difference was observed between P+ and P- on day 30. P4 increased significantly from day 60 to 80 and remained elevated until day 150 in P+, while remaining basal in P-. In FD and P- groups, P4 reached its lowest concentrations. A rapid decrease in P4 was observed in P- from day 20 onwards. A statistically significant difference in P4 was also noted between P+ and FD. Additionally, P4 concentrations differed between singleton and twin pregnancies, especially on days 20 and 40. Statistically significant differences in AMH were found between P+ and FD on days 10, 20, and 30. In P+ sheep, P4, AMH, and Hp concentrations varied by season. A significant relationship was found between AMH and Hp concentrations and body weight. In conclusion, P4 stands out as the primary marker for distinguishing pregnancy status and detecting embryonic loss, while AMH provides complementary support, particularly in identifying fetal death. Seasonal changes were reflected across P4, AMH, and Hp concentrations, with AMH and Hp also showing significant associations with BW.

ABSTRACT Slow‐release GnRH agonist implants containing deslorelin (SRI) are registered for temporary suppression of male fertility. The effect of SRI treatment on canine testicular function is well characterised, although the effect of downregulation and subsequent recovery on epididymal function has not been studied yet. Therefore, twenty‐nine healthy male dogs were treated with a 4.7 mg SRI for five months. Subsequent to implant removal, groups of 4–5 dogs were surgically castrated either at implant removal (week 0) or 2, 4, 6, or 10 weeks later. Three subgroups were categorised according to pre‐surgical testosterone levels. Five healthy untreated dogs served as control. Epididymides were separated into head, body and tail. Epididymal duct diameter and epithelial height were measured using haematoxylin–eosin‐stained sections of each dog and part of epididymides. Besides, the presence of spermatozoa, the cilial height, the thickness of the muscle layers and the relative amount of connective tissue were semiquantitatively assessed. The downregulated epididymis was characterised by a reduced epithelial height and epididymal duct diameter, lower cilia and absence of sperm, but more connective tissue, supporting that epididymal function is significantly altered by SRI treatment. At recovery subsequent to implant removal, the histomorphology was comparable with untreated controls. The study indicates that recovery of the epididymal function, like spermatogenesis, depends on testicular testosterone production.

The objective of this study was to evaluate structural echotexture changes in the uterine wall following abortion induction in bitches during the late embryonic/mid–gestation stage and to develop an evaluation method for the abortion process. A total of 10 healthy pregnant bitches of different breeds, ranging from 25 to 40 days (d) of gestation, were included in this study. In Group 1 (n=5), Aglepristone (10 mg·kg-1 bw, sc) was administered once daily for two consecutive d. In Group 2 (n=5), a combination of Aglepristone, Cabergoline, and Misoprostol was used for induction of abortion (IA). Prior to the induction of abortion, and at 24–hour intervals until completion of abortion (CA), the uterus and placenta were sonographically examined. Additional examinations were conducted on d 1 (CA+1), d 7 (CA+7), and d 14 (CA+14) after the abortion process was completed. Blood samples were taken on the same days to detect serum progesterone (P4) levels. Selected echotexture parameters (homogeneity, contrast, gradient, and entropy) were assessed on sonographical images using image analysis software (Bs200Pro®). Contrast and gradient values significantly decreased on d CA, CA+1 and CA+7 compared to the IA state (P<0.05 and P<0.01). Contrast values were lower in G1 than G2 two days before abortion (CA–2) (P<0.01). Gradient levels were higher in G2 than in G1 on CA–2 (P<0.01). Homogeneity values of G2 were higher than in G1 on d CA–1 and CA+7 (P<0.05). Progesterone values showed a non–significant decrease after IA during the study period in both groups. In G2, a negative correlation between P4 and homogeneity (r=-0.797) and a positive correlation between P4 and contrast values (r=0.719) were found. In conclusion, echotexture analysis allows quantitative and objective evaluation of the uterine structure during abortion, but specific standard values need to be established for both medication protocols, taking into account individual factors.

In this study, the expression and localization of gonadotropin-releasing hormone (GnRH1) and kisspeptin (KISS1) and their specific receptors in canine ovarian and uterine tissues were investigated after the application of deslorelin acetate (Suprelorin®, 4.7 mg, Virbac, France) in the late prepubertal period. We hypothesized that prolonged treatment of prepubertal dogs with deslorelin would alter the expression of GnRH and kisspeptin genes in the uterus and ovaries. Ovarian and uterine samples of 25 dogs with an average age of 7.8 ± 0.2 months and from mixed breeds were used. Following implant insertion, dogs entered estrus (EST; n = 6); dogs without estrus (N-EST; n = 10) comprised the experimental groups. Nine dogs with placebo implants served as a control (CONT). Ovarian and uterine tissues were investigated for expression of GnRH1, GnRHR, KISS1, and KISS1R/GPR54 mRNA and protein by using IHC and RT-qPCR. In the uterus, expression of GnRH1 significantly decreased in response to deslorelin treatment in the N-EST, compared with the control group. Compared with CONT, KISS1R expression in ovarian samples was significantly lower in the EST group. Uterine protein expression of GnRH1 appeared weaker in N-EST than in CONT. While GnRH1-system members and KISS1 protein were localized in the follicles at various stages and stroma, no or only weak signals were detected for KISS1R in the ovarian samples. Deslorelin-mediated induction of puberty by changing the expression of some of the GnRH and KISS1-system members seems to have an effect on ovarian and uterine functionality. Deslorelin implants can, therefore, not be considered a valuable alternative to induce fertile estrus in late-prepubertal bitches. However, further studies with a larger number of animals are needed to clarify the effect of deslorelin-mediated induction of puberty.

Slow-release gonadotropin-releasing hormone (GnRH) agonist implants are frequently used for contraception in male dogs. Although the effects are fully reversible, there is still concern about the safety of the implant's mode of action. Addressing this, we investigated cellular stress and androgen receptor (AR) signaling during downregulation and recovery. Testicular tissues were sampled from dogs castrated at different time points after GnRH implant removal and compared with untreated controls. AR, hypoxia-inducible factor 1 (HIF1A), heat shock proteins heat shock protein 72 (HSP72), heat shock protein 73 (heat shock cognate, HSPA8) (HSP73), heat shock protein A2 (HSPA2), heat shock protein 90 alpha (inducible isoform) (HSP90AA1), and heat shock protein 90 beta (constitutive isoform) (HSP90AB1) were investigated by quantitative real-time polymerase chain reaction and AR, HSP72, HSP73, and HSP90 immunohistochemically. While AR, HIF1A, and HSP70 were upregulated at gene expression level, HSPA8, HSPA2, and HSP90AA1 expression were downregulated during spermatogenic arrest; HSP90AB1 expression did not change. Immunohistochemistry verified AR-expression in Sertoli, peritubular, and Leydig cells, occasionally also in spermatogonia. Stress-inducible HSP72 was occasionally detected, while constitutive HSP73 and HSP90 were abundantly expressed by germ cells. Our results were similar to studies on seasonal breeders such as pine voles, geese, fish, and soft-shelled turtles. Accordingly, GnRH implants did not impose additional cellular stress on testicular cells when compared with natural recrudescence. Since comparative data on HIF1α are scarce, we cannot draw conclusions about hypoxic conditions.

This study was carried out by collecting tank milk samples every month, from a total of 240 farms producing cold chain milk for one year. Somatic cell count (SCC), total bacterial count (TBC), some nutritional elements (lactose, protein, casein, fat) and some physicochemical parameters (dry matter, fat–free dry matter, freezing point, density, free fatty acids, Soxhlet Henkel acidity degree) and citric acid were analyzed. According to the results; TBC were at the highest level in March (M), April (A) and June (J) (835.07 x103; 940.25 × 103 and 1007.30 × 103 cfu·mL–1), whereas between July (Ju) and December (De), TBC (446.09 × 103 and 795.15 × 103 cfu·mL–1) were significantly lower (P<0.001). The highest SCC were found in M, A and May (Ma), whereas the lowest SCC were found between September (S) and De. Between S and De, when SCC decreased, (varied between 236.13 × 103 cells·mL–1 and 284.43 × 103 cells·mL–1; P<0.05). Lactose values were found to be significantly higher in spring and summer compared to other months. A significant decrease was determined in protein values in the summer months compared to November (N) and De (P<0.05; P<0.01). It was also revealed that casein values were higher in the summer months Ma–August (Au) compared to the other lower months (P<0.01). For physico–chemical parameters, it was determined that non–fat solids and freezing point (FP) values decreased significantly during the summer months (P<0.01; P<0.001). The results obtained show that the parameters in question are seasonally affected, but these parameters change depending on the changes in both TBC and SCC values (high level of positive or negative correlation).

Abstract Objective Slow-release GnRH agonist implants (SRI) are used for reversible medical downregulation of testicular function in male dogs as an alternative to surgery. The 4.7 mg deslorelin SRI should reduce testosterone after 6–8 weeks and induce castration-like effects for 6 months (mon). However, some individual variation is described in the field in regard to onset and duration of effect. For this reason, we aimed to study the effects of the 4.7 mg deslorelin SRI in a larger cohort. Material and methods In total 50 intact, healthy male dogs (12–48 months, mon; 9–40 kg) were treated with a 4.7 mg deslorelin SRI into the umbilical area (TG, n=45) or served as untreated controls (CG, n=5). CG dogs were surgically castrated after measurement of testicular dimensions and blood sampling for testosterone. In TG, SRIs remained for 5 mon in place and subsequently 3–7 male dogs were surgically castrated at removal (week, W 0) or 1, 2, 3, 4, 5, 6, 7, 8 or 10 weeks later. Examination parameters were testicular dimensions (before treatment, at 4, 8, 12 W, 5 mon, weekly until castration), testosterone (before treatment, at 8 W, 5 mon, castration) and testicular histology (castration). Results Whereas examination parameters did not differ between CG and TG before treatment, testicular volume and testosterone was significantly reduced at all time points during treatment. In all but 3 (8 W) and 2 male dogs (5 mon) testosterone was basal during treatment before removal, whereas the parameters were significantly reduced compared to pre-treatment in the respective dogs. After implant removal, testosterone and testicular volumes increased. However, different to earlier studies, the „restart“ was more variable with individual basal testosterone until W7, but also physiological testosterone concentrations in W2. Similarly, histological testicular findings at castration were quite variable: besides an arrest on spermatogonia and spermatocytes, elongated spermatids with normal spermatogenesis were found in individual dogs. Conclusion Our study confirms the efficacy of the deslorelin SRI, but also individual variation especially regarding reversibility of effects on endocrine and germinative testicular function. Clinical relevance Deslorelin SRIs offer a suitable alternative to surgical castration with individual variation to be considered when used in clinical practice.

The canine placenta appears to have increased trophoblast-mediated inactivation of cortisol during mid-pregnancy, whereas parturition appears to be marked by increased local cortisol availability. Glucocorticoids modulate the feto-maternal interface during the induction of parturition. In the dog, the prepartum rise of cortisol in the maternal circulation appears to be erratic, and information about its contribution to the prepartum luteolytic cascade is scarce. However, the local placental upregulation of glucocorticoid receptor (GR/NR3C1) at term led to the hypothesis that species-specific regulatory mechanisms might apply to the involvement of cortisol in canine parturition. Therefore, here, we assessed the canine uterine/utero-placental spatio-temporal expression of hydroxysteroid 11-beta dehydrogenase 1 (HSD11B1; reduces cortisone to cortisol), and -2 (HSD11B2; oxidizes cortisol to the inactive cortisone). Both enzymes were detectable throughout pregnancy. Their transcriptional levels were elevated following implantation, with a strong increase in HSD11B2 post-implantation (days 18-25 of pregnancy), and in HSD11B1 at mid-gestation (days 35-40) (P < 0.05). Interestingly, when compared pairwise, HSD11B2 transcripts were higher during post-implantation, whereas HSD11B1 dominated during mid-gestation and luteolysis (P < 0.05). A custom-made species-specific antibody generated against HSD11B2 confirmed its decreased expression at prepartum luteolysis. Moreover, in mid-pregnant dogs treated with aglepristone, HSD11B1 was significantly higher than -2 (P < 0.05). HSD11B2 (protein and transcript) was localized mostly in the syncytiotrophoblast, whereas HSD11B1 mRNA was mainly localized in cytotrophoblast cells. Finally, in a functional approach using placental microsomes, a reduced conversion capacity to deactivate cortisol into cortisone was observed during prepartum luteolysis, fitting well with the diminished HSD11B2 levels. In particular, the latter findings support the presence of local increased cortisol availability at term in the dog, contrasting with an enhanced inactivation of cortisol during early pregnancy.

Mastitis is an important infection that affects herd health, udder health and milk yield of individual animals. Somatic cells (SCs) naturally present in milk are used as an indicator of subclinical mastitis, but also to assess milk quality and safety. Somatic cell count is the main monitoring variable used in milk quality and safety assessment. This review especially focuses on the effect of SCs on milk as food and also their effect on the dairy technology. The most significant effect of SCC on dairy technology is provided by the enzymes released from these cells. Alternatively, a limited number of conclusions were reported that SCs may assist dairy technology. SCs pass to milk and continue inhibitory effect on bacteria.

Although it is stated that there is an increase in calf loss rates at the global level and especially in modern dairy farms, this issue, which is an international animal welfare issue, has not been adequately defined at the national, large farm, or small farm level in most developing Countries. The rate of calf deaths before, during, and after birth is between 2–20% in heifers and cows. Previous studies showed that 75% of deaths occur during birth or within the first hour after birth, 10% before birth, and 15% within 48 hours after birth. This study aimed to determine the effect of Meloxicam administration on the quality of life and development of calves. An experimental method was used to achieve the aim of this research. A total of 60 Holstein calves, 30 in the experimental group and 30 in the control group, were included in the study for the study group. MELOXICAM (0.5 mg·kg-1) was administered to the mother cow and the calf immediately after birth, 2 days before the expected delivery. In this study, an 8 week process was passed to collect the data. It was concluded that Meloxicam did not affect the BHBA values of maternal cows. No calves died from pneumonia and diarrhea–related diseases after being treated with Meloxicam. From the total protein and total albumin values of the calves, it was concluded that Meloxicam did not affect the protein ratio, but did affect the albumin ratio. It was concluded that Meloxicam application increased the vital activity of calves.

To date, the biological functions of P4 within the canine placenta have been attributed to maternal stroma-derived decidual cells as the only placental cells expressing the nuclear P4 receptor (PGR). However, P4 can also exert its effects via membrane-bound receptors. To test the hypothesis that membrane-bound P4 receptors are involved in regulating placental function in the dog, the expression of mPRα, -β, -γ, PGRMC1 and -2 was investigated in the uterine and placental compartments derived from different stages of pregnancy and from prepartum luteolysis. Further, to assess the PGR signaling-mediated effects upon membrane P4 receptors in canine decidual cells, in vitro decidualized dog uterine stromal (DUS) cells were treated with type II antigestagens (aglepristone or mifepristone). The expression of all membrane P4 receptors was detectable in reproductive tissues and in DUS cells. The main findings indicate their distinguishable placental spatio-temporal distribution; PGRMC2 was predominantly found in decidual cells, PGRMC1 was strong in maternal endothelial compartments, and syncytiotrophoblast showed abundant levels of mPRα and mPRβ. In vitro decidualization was associated with increased expression of PGRMC1 and -2, while their protein levels were diminished by antigestagen treatment. The involvement of membrane-bound P4 signaling in the regulation of canine placental function is implied, with P4 effects being directly exerted through maternal and fetal cellular compartments. The indirect effects of PGR might involve the modulation of membrane-bound receptors availability in decidual cells, implying a self-regulatory loop of P4 in regulating the availability of its own receptors in the canine placenta.

BACKGROUND Non-steroidal anti-inflammatory drug (NSAID) use may cause diaphragm-like lesions in the bowel. Although NSAID-enteropathy is among the causes of protein-losing enteropathy (PLE), intractable hypoalbuminemia is rare. CASE REPORT Here, we discuss a case of NSAID-enteropathy with a diaphragm-like disease that presented with Protein Losing Enteropathy (PLE) rather than obstruction. The hypoalbuminemia recovered immediately after resection of the obstructive segment, despite ongoing annular ulcerations in the early postoperative period. Thus, it was not clear whether obstructive mechanisms influenced resistant hypoalbuminemia besides the ulcers. We also reviewed the English-written literature for "diaphragm-type lesion, NSAID-enteropathy, obstruction, and protein-losing enteropathy". We noted that the role of obstruction in the pathophysiology of PLE was not clear. CONCLUSIONS As our case and a couple of cases reported in literature, slow-onset obstructive pathology seems to contribute to well-known factors: inflammatory response, exudation, tight-junction dysfunction, and increase in permeability in the physiopathology of NSAID-induced PLE. Factors such as distention-induced low-flow ischemia and reperfusion, cholecystectomy-related continuous bile flow, bacterial overgrowth-related bile deconjugation and concomitant inflammation are among other potential influencers. The possible role of a slow-onset obstructive pathology in the physiopathology of NSAID-induced and other PLE needs to be further elucidated.