Dilated Lymphatic Vessels Research Articles

Podoplanin-positive dilated lymphatic vessels in duodenum predict three-month mortality in patients with cirrhosis

Background and Aim: Gut lymphatic vessels (LVs) regulate gut immunity and fluid homeostasis. In cirrhosis, dysfunctional gut LVs have been reported. Here, we studied LVs in duodenal (D2)-biopsies of liver cirrhosis patients and investigated the prognostic role of a LV-marker, podoplanin (pdpn) in predicting mortality of patients with cirrhosis.

Endothelial-specific depletion of TGF-\u03b2 signaling affects lymphatic function

BackgroundTransforming growth factor (TGF)-β is a multifunctional cytokine involved in cell differentiation, cell proliferation, and tissue homeostasis. Although TGF-β signaling is essential for maintaining blood vessel functions, little is known about the role of TGF-β in lymphatic homeostasis.MethodsTo delineate the role of TGF-β signaling in lymphatic vessels, TβRIIfl/fl mice were crossed with Prox1-CreERT2 mice to generate TβRIIfl/fl; Prox1-CreERT2 mice. The TβRII gene in the lymphatic endothelial cells (LECs) of the conditional knockout TβRIIiΔLEC mice was selectively deleted using tamoxifen. The effects of TβRII gene deletion on embryonic lymphangiogenesis, postnatal lymphatic structure and drainage function, tumor lymphangiogenesis, and lymphatic tumor metastasis were investigated.ResultsDeficiency of LEC-specific TGF-β signaling in embryos, where lymphangiogenesis is active, caused dorsal edema with dilated lymphatic vessels at E13.5. Postnatal mice in which lymphatic vessels had already been formed displayed dilation and increased bifurcator of lymphatic vessels after tamoxifen administration. Similar dilation was also observed in tumor lymphatic vessels. The drainage of FITC-dextran, which was subcutaneously injected into the soles of the feet of the mice, was reduced in TβRIIiΔLEC mice. Furthermore, Lewis lung carcinoma cells constitutively expressing GFP (LLC-GFP) transplanted into the footpads of the mice showed reduced patellar lymph node metastasis.ConclusionThese data suggest that TGF-β signaling in LECs maintains the structure of lymphatic vessels and lymphatic homeostasis, in addition to promoting tumor lymphatic metastasis. Therefore, suppression of TGF-β signaling in LECs might be effective in inhibiting cancer metastasis.

Dietary Exposure to the Food Contaminant Deoxynivalenol Triggers Colonic Breakdown by Activating the Mitochondrial and the Death Receptor Pathways.

The food contamination by mycotoxins is of increasing public health concerns. Deoxynivalenol (DON), a mycotoxin contaminating cereals, has been associated with the exacerbation of inflammatory bowel diseases (IBD), thereby raising the question of its role in the development of IBD. Moreover, the effect of DON on the colon is poorly described. Wistar rats exposed (1-4 weeks) to low doses of DON (2 or 9mg kg-1 feed) show microscopic alterations of colonic tissue (dilated lymphatic vessels, luminal debris, and cubic and flattened enterocytes). Ingestion of DON also alters colonic functions by increasing paracellular permeability while reducing the expression of the tight junction proteins and increased apoptosis in colonic tissue. Pro-apoptotic factors Bax/Bak, cytochrome C, and caspase 9 are upregulated, whereas expression of anti-apoptotic protein Bcl2 tends to decrease for the mitochondrial pathway. An increased expression of FasR and caspase-8 is observed for the extrinsic pathway. An increase in the pro-inflammatory markers TNFα, IL-17, and myeloperoxidase is also observed. These results indicate that the dietary exposure to low levels of DON in food targets the colon inducing a health-threatening breakdown of the colonic barrier, highlighting oral exposure to DON as a potential risk factor in triggering IBD.

Se-[(2,2-Dimethyl-1,3-dioxolan-4-yl)methyl] 4-Chlorobenzoselenolate Attenuates Inflammatory Response, Nociception, and Affective Disorders Related to Rheumatoid Arthritis in Mice.

Despite major advances, not all patients achieve rheumatoid arthritis (RA) remission, thus highlighting a pressing need for new therapeutic treatments. Given this scenario, this study sought to evaluate Se-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl] 4-chlorobenzoselenolate (Se-DMC) potential on a complete Freund's adjuvant (CFA)-induced unilateral arthritis model. The effects of Se-DMC (5 mg/kg; oral dose) and meloxicam (5 mg/kg; oral dose), both administered to animals daily for 14 days, on paw edema, mechanical sensitivity, neurobehavioral deficits (anxiogenic- and depressive-like behaviors), Na+/K+-ATPase activity, oxidative stress, and inflammation were evaluated in male Swiss mice exposed to CFA (intraplantar injection of 0.1 mL; 10 mg/mL). Se-DMC reduced the paw withdrawal threshold and CFA-induced paw edema. Histopathological results revealed the antiedematogenic potential of the compound, which was evidenced by lower quantities of dilated lymphatic vessels compared with the CFA group. Se-DMC reduced mRNA relative expression levels of tumor necrosis factor-α (TNF-α) and nuclear factor-κB (NF-κB) in the hippocampus and paw of CFA mice. The CFA-induced anxiogenic- and depressive-like behaviors were reversed by Se-DMC to the control levels in the elevated plus-maze and tail suspension tests. Se-DMC reduced the paw reactive species levels and restored the superoxide dismutase (hippocampus and paw) and Na+/K+-ATPase (hippocampus) activities previously increased by CFA. Moreover, CFA administration inhibited serum creatinine kinase activity, albeit the Se-DMC effects did not appear to involve the modulation of this enzyme and were equal to or greater than meloxicam. Se-DMC attenuates CFA-induced inflammatory response, nociception, and neurobehavioral deficits in mice.

A comparison of acute mouse hindlimb injuries between tourniquet- and femoral artery ligation-induced ischemia-reperfusion

The tourniquet or femoral artery ligation is widely used to stop extremity hemorrhage or create a bloodless operating field in the combat scenario and civilian setting. However, these procedures with subsequent reperfusion also induce ischemia-reperfusion (IR) injuries. To fully evaluate animal models of limb IR injuries, we compared tourniquet- and femoral artery ligation-induced IR injuries in the hindlimb of mice. In C57/BL6 mice, 3 h of unilateral hindlimb ischemia was induced by placement of a rubber band at the hip joint or a surgical ligation of the femoral artery. The tourniquet or femoral artery ligation was then released, allowing for 24 h of reperfusion. Compared to the femoral artery ligation/IR, the tourniquet/IR induced more severe skeletal muscle damage, including muscle necrosis and interruption of muscle fibers. There was no gastrocnemius muscle contraction in tourniquet/IR, while femoral artery ligation/IR markedly weakened gastrocnemius muscle contraction. Motor nerve terminals disappeared, and endplate potentials (EPPs) were undetectable in tourniquet/IR, whereas femoral artery ligation/IR only induced mild impairment of motor nerve terminals and decreased the amplitude of EPPs. Additionally, western blot data showed that proinflammatory cytokine levels (IL-1β and TNF-α) were higher in the tourniquet/IR than that in femoral artery ligation/IR. Moreover, tourniquet/IR caused significant tissue edema and dilation of lymphatic vessels in the hindlimb, compared to femoral artery ligation/IR. The above data demonstrated that tourniquet/IR-induced acute hindlimb injuries are more severe than those induced by femoral artery ligation/IR. This suggests that future investigators should determine which hindlimb IR model (tourniquet/IR or femoral artery ligation/IR) is optimal depending on the purpose of their study.

Canine Intestinal Lymphangiectasia Concomitant with Renal Cell Carcinoma

Abstract The etiology of dilation of lymphatic vessels, termed as intestinal lymphangiectasia, remains unknown. In most cases, it occurs secondary to other pathologic conditions such as gastrointestinal neoplasms. However, only a few cases of canine intestinal lymphangiectasia concurrent with non-gastrointestinal neoplasms have been reported so far. Moreover, the correlation between intestinal lymphangiectasia and non-gastrointestinal neoplasms has not been discussed in any other literature. In this study, we report a rare case of intestinal lymphangiectasia concomitant with renal cell carcinoma in an 11 year old female mixed Maltese, suggesting that non-gastrointestinal neoplasms could be associated with the development of intestinal lymphangiectasia. On gross observation, the small intestine was irregularly swollen presenting an accordion like shape. Microscopic examination revealed prominent dilatation of the lymphatic vessels, especially, within the submucosa and muscularis layer. The lacteals within the villi were dilated and presented “club-shaped” tips. The carcinoma might trigger intestinal lymphangiectasia by compressing the main lymphatic vessels or the cisterna chyli, subsequently increasing the pressure of the lymphatic vessels in the gastrointestinal tract. Moreover, metastasis of the carcinoma to the gastrointestinal tract could induce intestinal lymphangiectasia. Thus, the occurrence of intestinal lymphangiectasia must be considered when an abdominal neoplasm is located around major lymphatic vessels.

Prominent lymphatic vessel in a functioning bleb after repeat XEN gel stent implantation surgery in pseudoexfoliative glaucoma: a case report

XEN gel stent implantation (XEN) surgery is becoming more popular due to its safety profile and efficacy, with conjunctival lymphatics thought to be critical in maintaining bleb drainage. We are reporting the case of a 75-year-old man with right eye pseudoexfoliative glaucoma who had two previous episodes of failed XEN surgery despite given needling and antimetabolite. He had a repeat XEN surgery in our center and his intraocular pressure was under control at the time of writing without any topical glaucoma medication, needling, nor antimetabolite. On examination, there was presence of prominent, dilated, and irregular lymphatic vessel originating from the distal end of the bleb. Anterior segment optical coherence tomography identified the lymphatic vessel located in the superficial Tenon’s layer, which is most likely an initial lymphatic but larger in diameter. This dilated lymphatic vessel may be an important factor for his currently successful filtration surgery.

Pilomatricoma With Bullous Appearance: A Case Report

Introduction: Pilomatricoma is usually a solitary, deep dermal firm nodule with an overlying normal epidermis. Bullous pilomatricoma is rarely reported; thus, its pathogenesis has not been elucidated. We report a case presenting the pilomatricoma with bullous change. Case presentation: A 19-year-old female presented a firm nodule covered by a bulla on her right upper arm. Histopathological examination showed the tumor was composed of basophilic basal-like cells and shadow cells. No cellular atypia or abnormal mitotic figures were observed. All these clinical characteristics and pathological results point to the diagnosis of bullous pilomatricoma. The tumor was surgically removed by enlargement. Discussion: We hypothesize that a history of trauma and rapid growth may contribute to the diagnosis of the bullous pilomatricoma. The appearance of the bullous can be explained by the dilated lymphatic vessels seen in histopathologic examination. We give a case report help clinicians to better diagnose this entity and decrease the rate of misdiagnosis. Conclusion: We observed a rare bullous variant of pilomatricoma. Hence, when identifying a patient of bullous pilomatricoma, a detailed medical history and physical examination are essential.

Overview on pathogenesis and histopathological observations of hyperostosis in two fish species; Scomberoides lysan (Forsskal, 1775) and Pomacanthus sextriatus (Cuvier, 1831) collected from El- Jubail province, Saudi Arabia

During years 2012 to 2018, two fish species, doublespotted queenfish (Scomberoides lysan) and sixbar angelfish (Pomacanthus sextriatus) were regularly examined during filleting processing in fish markets at Jubail province, Saudi Arabia. The routine fish inspection of the fillet- by products (fish skeletons) of these two species showed prominent and frequent hard circumscribed ossified masses attached to the spines. In Scomberoides lysan 60% of the examined fishes were affected and the hyperosteoid overgrowths were noticed in both haemal and neural spines. In Pomacanthus sextriatus 10% showed nearly the same lesion but it was mainly observed in the neural spines. In gross examination, the swelling appeared very hard, round and smooth; the cut section showed grayish- white, granular, greasy and hard central contents. In histopathological examination, the hard masses showed hyperosteoid bony tissue with variable degrees of ossification surrounded with peripheral fibrous tissue capsule containing dilated lymph and blood vessels and accompanied with edema. The underlying tissue was a thick layer of acellular calcified bony tissue while the central area of the swelling was honeycomb in its appearance with cavities filled with blood and adipocytes together with golden brown pigments, hemosiderin. Our study concluded that hyperostosis occurs at high prevalence rates in S. lysan and P. sextriatus with characteristic histopathological lesions.

Saireito Improves Lymphatic Function and Prevents UVB-Induced Acute Inflammation and Photodamage in HR-1 Hairless Mice.

A single high-dose ultraviolet B (UVB) exposure on the skin induces acute inflammatory responses, such as an increase in proinflammatory cytokines (e.g., IL-6 and IL-1β), hyperpermeability and dilation of blood and lymphatic vessels, and infiltration of inflammatory cells. These responses result in different cutaneous disorders characterized by erythema, epidermal hyperplasia, edema formation, and extracellular matrix degradation. Saireito extract (SRT), a traditional Chinese medicine, has been used to treat various inflammatory diseases in Japan, and SRT and its major active components (e.g., saikosaponins and baicalin) were reported to downregulate proinflammatory cytokines. Moreover, SRT has a protective effect against UV irradiation in vitro. Based on these findings, we aimed to investigate the effect of SRT on UVB-induced photodamage and structural change in the vasculature. We pretreated male HR-1 hairless mice with SRT (625 or 1250 mg/kg) for 3 weeks before a single UVB (250 mJ/cm2) irradiation. SRT treatment attenuated UVB-induced increases in erythema, transepidermal water loss, and edema formation at 72 h after irradiation. SRT treatment also suppressed UVB-induced inflammatory cell infiltration and collagen degradation. Furthermore, at 24 h after irradiation, SRT treatment inhibited UVB-induced upregulation of proinflammatory cytokines and reduction in lymphatic vessel density associated with upregulation of VEGF-C expression. These results suggest that SRT could attenuate UVB-induced photodamage. This protective effect of SRT involves suppression of upregulation of proinflammatory cytokines and improvement of lymphatic function in the early stage of inflammation.

Hair follicle stem cells as a skin-organizing signaling center during adult homeostasis.

Stem cells are the essential source of building blocks for tissue homeostasis and regeneration. Their behavior is dictated by both cell-intrinsic cues and extrinsic cues from the microenvironment, known as the stem cell niche. Interestingly, recent work began to demonstrate that hair follicle stem cells (HFSCs) are not only passive recipients of signals from the surroundings, but also actively send out signals to modulate the organization and function of their own niches. Here, we discuss recent findings, and briefly refer to the old, on the interaction of HFSCs and their niches with the emphasis on the outwards signals from HFSCs toward their niches. We also highlight recent technology advancements that further promote our understanding of HFSC niches. Taken together, the HFSCs emerge as a skin-organizing center rich in signaling output for niche remodeling during various stages of adult skin homeostasis. The intricate crosstalk between HFSCs and their niches adds important insight to skin biology that will inform clinical and bioengineering fields aiming to build complete and functional 3D organotypic cultures for skin replacement therapies.

The Potential Teratogenic Effect of Tilmicosin in Rats: Visceral Malformations and Histomorphological Alterations in Fetal Internal Organs

Potential fetal adverse effects are well-known for several antibacterial classes. The present study was performed to evaluate the potential teratogenic effect of Tilmicosin (TMS) antibiotic in Sprague Dawley rats. TMS was daily administered orally to pregnant rats at two dose levels, 250 or 500 mg/kg bw, on 6-15 days of gestation. The morphological or skeletal malformations were non-significantly different from control values. However, visceral examination revealed elevation in the percentage of intrathoracic and intracranial haemorrhages, and kidney hypoplasia (unilateral or bilateral) in fetuses from dams treated with the high dose. In addition, both dose levels produced fetuses with increased percentages of dilated brain ventricles, heart ventricles and renal pelvis. Histopathologically, both TMS doses induced pathological changes in fetal liver and kidney, in a dose-dependent manner. Liver showed hepatocyte hydropic degeneration, congestion of hepatic blood vessels, engorgement of bile canaliculi and dilatation of hepatic lymphatic vessels. Kidney revealed coagulative necrosis of renal tubules and glomerular tuft, adhesion between the parietal and visceral layers of Bowman’s capsule and the glomerular tuft became ring shape with the presence of multiple layer glomerular tufts. In conclusion, TMS antibiotic has the potential to induce teratogenic effects (mainly visceral) and pathological changes in liver and kidneys tissues of rat fetuses when administered during the organogenesis period. This result demonstrated the ability of TMS to pass the placental barrier.

Gallbladder cholesterolosis in patients with metabolic syndrome and chronic pancreatitis

Cholesterolosis, as a pathological condition caused by metabolic disorders, is potentially associated with metabolic syndrome and chronic pancreatitis. The aim of the study was to assess the prevalence and morphological features of gallbladder cholesterolosis in the contingent of patients with metabolic syndrome and chronic pancreatitis. 82 patients who underwent cholecystectomy for chronic calculous cholecystitis were included in our study. The experimental group consisted of 37 patients with metabolic syndrome and chronic pancreatitis. The comparison group included 45 patients without clinically confirmed metabolic syndrome and chronic pancreatitis. In accordance with the purpose and objectives, morphological examination of the gallbladder wall was performed. Data to be analyzed were processed using the statistical software package SPSS 20.0 for Windows. The gender and age structure of the studied contingent did not differ from that described in the scientific literature. The morphological picture of cholesterolosis did not differ in the study groups. In a mucous membrane considerable polymorphism of folds (villi) was noted. There were signs of desquamation and regeneration in the epithelium. There was a violation of the structure Rokitansky-Aschoff sinuses. In some crypts microconcretions were defined. Atrophy and sclerosis of the stroma of the villi were detected in the mucous membrane. Significant expansion of the lumen of the veins in the own plate of the mucous membrane and the perimuscular layer of the gallbladder wall was noteworthy. Signs of stasis were found in the lumen of blood vessels. The lumen of the arteries was narrowed in places due to swelling and accumulation of yellow-brown pigment. Signs of spasm and significant sclerosis of the wall were identified. Dystrophic changes in the endothelium contribute not only to the development of uneven plethora of stagnant nature with significant edema, but also hemorrhage. Significant swelling of all layers was characteristic, causing their disintegration. Significant dilation of lymphatic vessels causes a significant thickening of the gallbladder wall. In some places, there is uneven hypertrophy of the muscle layer. There was an excessive increase in the tortuosity ducts of Luschka. According to the study, patients with metabolic syndrome and chronic pancreatitis, operated on for chronic calculous cholecystitis, along with maintaining the gender and age structure of the contingent, there is a significantly higher incidence of gallbladder cholesterolosis.

Dilatation of lymphatic vessels increases liver stiffness on transient elastography irrespective of fibrosis.

Liver stiffness measured using transient elastography (TE) is affected by tissue viscosity. The role of intrahepatic lymphatic fluid in liver stiffness is unclear. The present study aimed to investigate the effects of lymphatic vessel dilatation on liver stiffness. Patients with chronic liver disease (n=116) were enrolled from June 2018 to March 2020. All specimens were acquired by laparoscopic liver biopsy. Biopsy samples were stained with D2-40 for lymphatic vessel quantification based on a five-point scale for each specimen. Independent associations of liver stiffness measured by TE, strain elasticity (liver fibrosis index), and controlled attenuation parameter with fibrosis, lymphatic vessels, alanine aminotransferase, bilirubin, and steatosis were evaluated. Fibrosis, splenic stiffness measurement, and splenic volume were significantly correlated with the area of lymphatic vessels. Fibrosis, lymphatic vessels, and alanine aminotransferase were independent factors significantly associated with liver stiffness measurement (LSM; standardized coefficient [β]=0.375, P<0.001; β=0.342, P<0.001; and β=0.359, P<0.001, respectively). Fibrosis was the only independent factor significantly associated with liver fibrosis index (β=0.360, P<0.001), whereas the fat deposit area was the only independent factor significantly associated with controlled attenuation parameter (β=0.455, P<0.001). The areas under the receiver operating characteristic curves for diagnosing controlled ascites based on LSM, liver fibrosis index, splenic stiffness measurement, collagen proportionate area, and area of lymphatic vessels were 0.94, 0.66, 0.76, 0.64, and 0.79, respectively. Lymphatic vessel dilatation can affect liver stiffness measured using TE. Liver stiffness measurement is a predictive factor for ascites.

Lymphatic muscle cells contribute to dysfunction of the synovial lymphatic system in inflammatory arthritis in mice

BackgroundOur previous studies reveal that impaired draining function of the synovial lymphatic vessel (LV) contributes to the pathogenesis of inflammatory arthritis, but the cellular and molecular mechanisms involved are not fully understood.ObjectiveTo investigate the involvement of lymphatic muscle cells (LMCs) in mediating impaired LV function in inflammatory arthritis.MethodsTNF transgenic (TNF-Tg) arthritic mice were used. The structure and function of the LVs that drained the hind limbs were examined by whole-mount immunofluorescence staining, electron microscopy, and near-infrared lymphatic imaging. Primary LMCs were treated with TNF, and the changes in proliferation, apoptosis, and functional gene expression were assessed. The roles of the herbal drug, Panax notoginseng saponins (PNS), in arthritis and LVs were studied.ResultsTNF-Tg mice developed ankle arthritis with age, which was associated with abnormalities of LVs: (1) dilated capillary LVs with few branch points, (2) mature LVs with reduced LMC coverage and draining function, and (3) degenerative and apoptotic appearance of LMCs. TNF caused LMC apoptosis, reduced expression of muscle functional genes, and promoted the production of nitric oxide (NO) by lymphatic endothelial cells (LECs). PNS attenuated arthritis, restored LMC coverage and draining function of mature LVs, inhibited TNF-mediated NO expression, and reduced LMC apoptosis.ConclusionThe impaired draining function of LVs in TNF-Tg mice involves LMC apoptosis. TNF promotes LMC death directly and indirectly via NO production by LECs. PNS attenuates arthritis, improves LVs, and prevents TNF-induced LMC apoptosis by inhibiting NO production of LECs. LMCs contribute to the dysfunction of synovial LVs in inflammatory arthritis.

Ultrasound and endoscopic findings in dogs with lymphangiectasia

ABSTRACT Lymphangiectasia is a heterogenous inflammatory bowel disease characterized by lymphatic vessel dilation, chronic diarrhea and protein loss such as serum albumin and globulin. The most common cause of lymphangiectasia is considered to be the congenital malformation of the lymphatics. The study was conducted between 2012-2015 on 76 dogs suffering from intestinal disorders and manifesting digestive symptoms such as diarrhea or weight loss. In order to assess the origin of disorder, physical examination, biochemistry profile, ultrasound and endoscopic examinations were performed. Ultrasound examination tried to assess the changes of intestines’ echogenicity, changes in wall thickness, wall layering and presence of striations or / and speckles (hyperechoic structures along intestinal mucosal layer). Endoscopic examination findings included dilated lacteals (59.2%) and erythema (21.1%). Although increased friability was observed in 33 dogs, it was not considered in the study due to limitations represented by the evaluation of the endoscopic images only. The study proved that an extremely significant statistical correlation exists between the presence of speckles and dilated lacteals in dogs with lymphangiectasia (P&lt;0.05). Up to now, there is no other study to make an association between the white spots observed in ultrasound examination and dilated lacteals revealed after endoscopy in dogs with intestinal lymphangiectasia.

Lymphaticovenous anastomosis for advanced-stage lower limb lymphedema.

Early-stage lymphedema patients are said to be candidates for lymphaticovenous anastomosis (LVA). The progressions in the preoperative examinations have made it possible to find the suitable lymphatic vessels even in advanced-stage lymphedema. The aim of this study was to elucidate the surgical effect of LVA in cases of advanced-stage lymphedema. We evaluated 42 limbs of 34 patients with lymphoscintigraphic type 4 or 5. A mean disease duration was 7.5 ± 6.5 years. We performed multi-lymphosome indocyanine green (ICG) lymphography preoperatively to detect the saphenous lymphatics, the lateral calf lymphatics, and the lateral thigh lymphatics. We also performed ultrasound to detect the subcutaneous veins and the dilated lymphatic vessels. The pre- and postoperative evaluation was made by the sum of circumference measurements at 6 points per limb. The mean number of anastomosis per limb was 2.8 (range, 1-5). Of the 41 limbs for which we performed ICG lymphography, we found the saphenous lymphatics in 29 limbs (70.7%), lateral calf lymphatics in 28 limbs (68.3%), and lateral thigh lymphatics in 21 limbs (51.2%). We found at least 1 linear pattern in ICG lymphography for 39 limbs (95.1%). The mean pre- and postoperative circumference (sum of 6 points) were 221.7 ± 4.9 cm and 215.9 ± 4.9 cm, which was significantly reduced (p < .01). LVA was effective for advanced-stage lymphedema patients. An adequate preoperative examination with plural imaging methods seems helpful for achieving a successful surgical result.

A preliminary observational study on the vascular, nerve, and lymphatic anatomy and histology of the labia minora from cadaveric and surgical samples.

To better understand details of the fine anatomy of the labia minora, present images of the vascular anatomy and characterize the nerve and lymphatic distribution of the labia minora. Two fixed and five fresh cadaveric specimens were perfused and dissected, and the vascular network was photographed. Labia minora samples, prepared from cadavers, and tissue resulting from labia reduction surgery underwent hematoxylin and eosin staining and S100 and D2-40 immunohistochemical staining. Arteries emanated from the base to the edge of the labia minora, where there was a larger feeding artery, and the arteries were anastomosed. The veins formed anastomotic branches in the same direction as the edge of the labia minora. Arteries and veins that accessed the labia minora were successfully perfused at the same time with no obvious association. Sensory nerve endings were abundant, mostly larger with myelinated nerve trunks and Schwann cells in the central area with suggested neurovascular associations and smaller with no obvious aggregation at the edge. The medial area had 23.63 ± 11.82 nerves/view, the lateral area 21.30 ± 11.49 nerves/view (P > 0.05). The thickest nerve bundle was 3.16 ± 1.41mm from the medial epidermis and 3.13 ± 1.47mm from the lateral epidermis. Lymphatic vessels showed no obvious regional distribution. Labia minora were 21.77 ± 5.69mm wide with 252.87 ± 63.01 lymphatic vessels at 3.67 ± 1.61/mm2 density. The shortest inner diameter of dilated lymphatic vessels was 161.09 ± 49.99 μm. A larger feeding artery exists in the labia minora, which should be noticed in the pre-surgery design of labiaplasty. No difference was observed in the nerve distribution between the medial and lateral sides. Lymphedema might not be the cause of labial hypertrophy.

Degradation of lymphatic anatomy and function in early venous insufficiency

ObjectiveWe used near-infrared fluorescence lymphatic imaging in a pilot study to assess the lymphatics in preulcerative (C2-C4) venous insufficiency and determine whether involvement and/or degradation of lymphatic anatomy or function could play a role in the progression of chronic venous insufficiency. We also explored the role of lymphatics in early peripheral arterial disease. MethodsAfter informed consent and intradermal injections of indocyanine green for rapid lymphatic uptake, near-infrared fluorescence lymphatic imaging was used to assess the lymphatic anatomic structure and quantify the lymphatic propulsion rates in subjects with early venous insufficiency. The anatomic observations included interstitial backflow, characterized by the abnormal spreading of indocyanine green from the injection site primarily into the surrounding interstitial tissues; dermal backflow, characterized by the retrograde movement of dye-laden lymph from collecting lymphatics into the lymphatic capillaries; and lymphatic vessel segmentation and dilation. ResultsTen subjects with venous insufficiency were enrolled, resulting in two legs with C2 disease, nine legs with C3 disease, eight legs with C4 disease, and one leg with C5 disease. Interstitial and/or dermal backflow were observed in 25%, 33%, and 41% of the injection sites in each limb with C2, C3, and C4 disease, respectively. Distinct vessel segmentation and dilation were observed in limbs with a C3 and higher classification, and dermal backflow proximal to the injection sites was observed in two legs with C4 disease and in the inguinal region of the C5 study subject. The overall average lymph propulsion rates were 1.3 ± 0.4, 1.2 ± 0.7, and 0.8 ± 0.5 contractile events/min for limbs with C2, C3, and C4 disease, respectively. One subject with peripheral arterial disease, who had previously undergone bypass surgery, presented with extensive dermal backflow and lymphatic reflux. ConclusionsNear-infrared fluorescence lymphatic imaging demonstrated that, compared with normal health subjects, the lymphatic anatomy and contractile function generally degrade with the severity of venous insufficiency. Lymphatic abnormalities mimic those in early cancer-acquired lymphedema subjects, as previously observed by us and others. Additional studies are needed to decipher the relationship, including any causality, between lymphatic dysfunction and peripheral vascular disease and venous insufficiency.

The Role of Hydrogen Sulfide in the Dilatation of Mesenteric Lymphatic Vessels in Bulls.

We studied the effects and mechanisms of action of NaHS, an H2S donor, on bovine isolated mesenteric efferent lymphatic vessels pre-contracted with phenylephrine. NaHS induced concentration-dependent relaxation of lymphatic vessels. Removal of the endothelium reduced, but did not completely abolish the relaxing effect of NaHS. Application of NO synthase inhibitor L-NAME, soluble guanylyl cyclase inhibitor ODQ, blocker ATP-sensitive K+ channels glibenclamide, and a combination of blockers of Ca-activated K+ channels of small and intermediate conductance charybdotoxin and apamin attenuated relaxation of lymphatic vessels. Thus, H2S produces a pleiotropic effect on lymphatic vessels; vasorelaxant effect is achieved by several parallel mechanisms. H2S induces relaxation of lymphatic vessels and modulates the rate of lymph transport, thereby affecting the development of immune processes in the body.